Breast Cancer

Ultrasound for assessing lymph nodal involvement may be substituted for sentinel lymph node biopsy with no change in outcomes in patients with early breast cancer, a new study finds.

This was the conclusion of research on the agenda at the American Society of Breast Surgeons annual meeting.

Sentinel lymph node biopsy (SLNB) is the standard of care for individuals with early-stage HR+HER2- breast cancer to assess nodal involvement, but SLNB can bring complications including postoperative arm problems and lasting lymphedema, according to Andreas Giannakou, MD, of Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, the presenter of this new research.

The SOUND (Sentinel Node vs. Observation After Axillary Ultra-Sound) trial, published in JAMA Oncology in 2023, showed that ultrasound nodal imaging was a safe and effective alternative to SLNB in certain patients with early-stage breast cancers, but real-world validation was needed, Dr. Giannakou said during a press briefing in advance of the meeting.

Why Was the SOUND Trial Important?

The SOUND trial randomized 1,463 individuals with early stage (cT1NO) breast cancer (tumors less than 2 cm) and negative findings on axillary ultrasound to either SLNB or no axillary surgical staging.

The 5-year rate of distant disease-free survival was 97.7% in the SLNB group vs. 98% in the no axillary surgery group, suggesting that omission of staging was noninferior to SLNB in these patients and a safe and effective option.

In current practice, nodal status remains a key factor in decision-making for adjuvant systemic therapy in premenopausal patients and in patients with HER2+ and triple-negative breast cancer, Dr. Giannakou said during the press briefing.

“The SOUND trial is a potentially practice-changing study that can spare a specific patient population from axillary surgical staging,” Dr. Giannakou said in an interview. “Before broadly applying clinical trial results to practice, it is important to ensure that the trial population is representative of the population being treated in real world practice,” he said.

What Did the New Study Show? 

In the new study, the researchers identified 312 patients meeting the SOUND trial eligibility criteria in a large database from a single center, and compared disease characteristics and outcomes with the 708 patients in the SLNB arm of the SOUND trial.

The researchers found a similarly high rate of negative SLNB results and very low recurrence in the study population. Notably, only 11.3% of the patients in the current study and 13.1% of patients in the SOUND trial had 1-3 positive lymph nodes, and less than 1% of patients in both cohorts had 4 or more positive nodes, Dr. Giannakou said.

The population of the current study was similar to that of the SOUND trial population with respect to treatment characteristics and nodal disease burden,” Dr. Giannakou said during the interview. These findings suggest that omission of sentinel lymph node in the new study cohort would have also likely been oncologically safe.

“These results are confirmatory but not surprising,” he said. Previous studies have shown that the sensitivity and accuracy of axillary ultrasound is comparable to the sentinel lymph node biopsy in patients with early breast cancer and only one abnormal lymph node on the ultrasound. 
 

What Are the Clinical Implications?

The current study findings make an important contribution to the effort to de-escalate axillary surgery in early breast cancer, Dr. Giannakou said during the interview. Although SLNB is less morbid than axillary lymph node dissection, the lymphedema risk still exists, and identifying which patients actually benefit from SLNB is critical, he said.

“In our multidisciplinary team, we are working to define selection criteria for postmenopausal patients with HR+HER2- breast cancer who would have met eligibility criteria for the SOUND trial and for whom omission of SLNB would not change adjuvant treatment considerations,” he said.

“Breast surgeons have been moving towards less aggressive axillary surgery based on evidence showing its safety in specific patient cohorts, particularly those with low-risk factors such as older age (70 years and above) and early-stage hormone receptor-positive breast cancer,” Sarah Blair, MD, professor and vice chair in the department of surgery at UC San Diego Health, said in an interview.

“The Choosing Wisely recommendations, issued by the Society of Surgical Oncology, advise against routine use of sentinel lymph node biopsy in women aged 70 and older with early-stage hormone receptor–positive breast cancer; these recommendations are based on clinical trials demonstrating oncologic safety in this population,” said Dr. Blair, who was not involved in the SOUND trial or the current study.

The data from the new study are encouraging and highlight the generalizability of the SOUND results, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said in an interview. The results help to define a low-risk group of patients for which sentinel node staging may be omitted, after multidisciplinary discussion to ensure that nodal staging will not impact adjuvant systemic therapy or radiation decision-making, said Dr. Teshome, who was not involved in the SOUND trial or the current study.
 

What Are the Limitations of the SOUND trial and the New Study?

The current study limitations included its design having been a retrospective review of a prospective database with selection bias, lack of standard criteria for preoperative axillary ultrasound, and the lack of SLNB for many patients older than 70 years based on the Choosing Wisely criteria, Dr. Giannakou said in the press briefing.

“Despite the evidence supporting axillary surgery de-escalation, it can be challenging for surgeons to change their practice based on a single study,” Dr. Blair said an interview. However, the SOUND trial findings support current evidence, giving surgeons more confidence to discuss multidisciplinary treatment options, she said.
 

What Additional Research is Needed?

“Longer follow-up is needed to make definitive conclusions about the oncologic outcomes of axillary surgery de-escalation in this patient population,” said Dr. Blair. “Given that slow-growing tumors are involved, the time to recurrence may extend beyond the typical follow-up period of three years.

“Ongoing research and collaboration among multidisciplinary teams are essential to ensure optimal treatment decisions and patient outcomes,” she emphasized.

Dr. Giannakou, Dr. Blair, and Dr. Teshome had no financial conflicts to disclose.

Ultrasound for assessing lymph nodal involvement may be substituted for sentinel lymph node biopsy with no change in outcomes in patients with early breast cancer, a new study finds.

This was the conclusion of research on the agenda at the American Society of Breast Surgeons annual meeting.

Sentinel lymph node biopsy (SLNB) is the standard of care for individuals with early-stage HR+HER2- breast cancer to assess nodal involvement, but SLNB can bring complications including postoperative arm problems and lasting lymphedema, according to Andreas Giannakou, MD, of Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, the presenter of this new research.

The SOUND (Sentinel Node vs. Observation After Axillary Ultra-Sound) trial, published in JAMA Oncology in 2023, showed that ultrasound nodal imaging was a safe and effective alternative to SLNB in certain patients with early-stage breast cancers, but real-world validation was needed, Dr. Giannakou said during a press briefing in advance of the meeting.

Why Was the SOUND Trial Important?

The SOUND trial randomized 1,463 individuals with early stage (cT1NO) breast cancer (tumors less than 2 cm) and negative findings on axillary ultrasound to either SLNB or no axillary surgical staging.

The 5-year rate of distant disease-free survival was 97.7% in the SLNB group vs. 98% in the no axillary surgery group, suggesting that omission of staging was noninferior to SLNB in these patients and a safe and effective option.

In current practice, nodal status remains a key factor in decision-making for adjuvant systemic therapy in premenopausal patients and in patients with HER2+ and triple-negative breast cancer, Dr. Giannakou said during the press briefing.

“The SOUND trial is a potentially practice-changing study that can spare a specific patient population from axillary surgical staging,” Dr. Giannakou said in an interview. “Before broadly applying clinical trial results to practice, it is important to ensure that the trial population is representative of the population being treated in real world practice,” he said.

What Did the New Study Show? 

In the new study, the researchers identified 312 patients meeting the SOUND trial eligibility criteria in a large database from a single center, and compared disease characteristics and outcomes with the 708 patients in the SLNB arm of the SOUND trial.

The researchers found a similarly high rate of negative SLNB results and very low recurrence in the study population. Notably, only 11.3% of the patients in the current study and 13.1% of patients in the SOUND trial had 1-3 positive lymph nodes, and less than 1% of patients in both cohorts had 4 or more positive nodes, Dr. Giannakou said.

The population of the current study was similar to that of the SOUND trial population with respect to treatment characteristics and nodal disease burden,” Dr. Giannakou said during the interview. These findings suggest that omission of sentinel lymph node in the new study cohort would have also likely been oncologically safe.

“These results are confirmatory but not surprising,” he said. Previous studies have shown that the sensitivity and accuracy of axillary ultrasound is comparable to the sentinel lymph node biopsy in patients with early breast cancer and only one abnormal lymph node on the ultrasound. 
 

What Are the Clinical Implications?

The current study findings make an important contribution to the effort to de-escalate axillary surgery in early breast cancer, Dr. Giannakou said during the interview. Although SLNB is less morbid than axillary lymph node dissection, the lymphedema risk still exists, and identifying which patients actually benefit from SLNB is critical, he said.

“In our multidisciplinary team, we are working to define selection criteria for postmenopausal patients with HR+HER2- breast cancer who would have met eligibility criteria for the SOUND trial and for whom omission of SLNB would not change adjuvant treatment considerations,” he said.

“Breast surgeons have been moving towards less aggressive axillary surgery based on evidence showing its safety in specific patient cohorts, particularly those with low-risk factors such as older age (70 years and above) and early-stage hormone receptor-positive breast cancer,” Sarah Blair, MD, professor and vice chair in the department of surgery at UC San Diego Health, said in an interview.

“The Choosing Wisely recommendations, issued by the Society of Surgical Oncology, advise against routine use of sentinel lymph node biopsy in women aged 70 and older with early-stage hormone receptor–positive breast cancer; these recommendations are based on clinical trials demonstrating oncologic safety in this population,” said Dr. Blair, who was not involved in the SOUND trial or the current study.

The data from the new study are encouraging and highlight the generalizability of the SOUND results, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said in an interview. The results help to define a low-risk group of patients for which sentinel node staging may be omitted, after multidisciplinary discussion to ensure that nodal staging will not impact adjuvant systemic therapy or radiation decision-making, said Dr. Teshome, who was not involved in the SOUND trial or the current study.
 

What Are the Limitations of the SOUND trial and the New Study?

The current study limitations included its design having been a retrospective review of a prospective database with selection bias, lack of standard criteria for preoperative axillary ultrasound, and the lack of SLNB for many patients older than 70 years based on the Choosing Wisely criteria, Dr. Giannakou said in the press briefing.

“Despite the evidence supporting axillary surgery de-escalation, it can be challenging for surgeons to change their practice based on a single study,” Dr. Blair said an interview. However, the SOUND trial findings support current evidence, giving surgeons more confidence to discuss multidisciplinary treatment options, she said.
 

What Additional Research is Needed?

“Longer follow-up is needed to make definitive conclusions about the oncologic outcomes of axillary surgery de-escalation in this patient population,” said Dr. Blair. “Given that slow-growing tumors are involved, the time to recurrence may extend beyond the typical follow-up period of three years.

“Ongoing research and collaboration among multidisciplinary teams are essential to ensure optimal treatment decisions and patient outcomes,” she emphasized.

Dr. Giannakou, Dr. Blair, and Dr. Teshome had no financial conflicts to disclose.

Ultrasound for assessing lymph nodal involvement may be substituted for sentinel lymph node biopsy with no change in outcomes in patients with early breast cancer, a new study finds.

This was the conclusion of research on the agenda at the American Society of Breast Surgeons annual meeting.

Sentinel lymph node biopsy (SLNB) is the standard of care for individuals with early-stage HR+HER2- breast cancer to assess nodal involvement, but SLNB can bring complications including postoperative arm problems and lasting lymphedema, according to Andreas Giannakou, MD, of Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, Boston, the presenter of this new research.

The SOUND (Sentinel Node vs. Observation After Axillary Ultra-Sound) trial, published in JAMA Oncology in 2023, showed that ultrasound nodal imaging was a safe and effective alternative to SLNB in certain patients with early-stage breast cancers, but real-world validation was needed, Dr. Giannakou said during a press briefing in advance of the meeting.

Why Was the SOUND Trial Important?

The SOUND trial randomized 1,463 individuals with early stage (cT1NO) breast cancer (tumors less than 2 cm) and negative findings on axillary ultrasound to either SLNB or no axillary surgical staging.

The 5-year rate of distant disease-free survival was 97.7% in the SLNB group vs. 98% in the no axillary surgery group, suggesting that omission of staging was noninferior to SLNB in these patients and a safe and effective option.

In current practice, nodal status remains a key factor in decision-making for adjuvant systemic therapy in premenopausal patients and in patients with HER2+ and triple-negative breast cancer, Dr. Giannakou said during the press briefing.

“The SOUND trial is a potentially practice-changing study that can spare a specific patient population from axillary surgical staging,” Dr. Giannakou said in an interview. “Before broadly applying clinical trial results to practice, it is important to ensure that the trial population is representative of the population being treated in real world practice,” he said.

What Did the New Study Show? 

In the new study, the researchers identified 312 patients meeting the SOUND trial eligibility criteria in a large database from a single center, and compared disease characteristics and outcomes with the 708 patients in the SLNB arm of the SOUND trial.

The researchers found a similarly high rate of negative SLNB results and very low recurrence in the study population. Notably, only 11.3% of the patients in the current study and 13.1% of patients in the SOUND trial had 1-3 positive lymph nodes, and less than 1% of patients in both cohorts had 4 or more positive nodes, Dr. Giannakou said.

The population of the current study was similar to that of the SOUND trial population with respect to treatment characteristics and nodal disease burden,” Dr. Giannakou said during the interview. These findings suggest that omission of sentinel lymph node in the new study cohort would have also likely been oncologically safe.

“These results are confirmatory but not surprising,” he said. Previous studies have shown that the sensitivity and accuracy of axillary ultrasound is comparable to the sentinel lymph node biopsy in patients with early breast cancer and only one abnormal lymph node on the ultrasound. 
 

What Are the Clinical Implications?

The current study findings make an important contribution to the effort to de-escalate axillary surgery in early breast cancer, Dr. Giannakou said during the interview. Although SLNB is less morbid than axillary lymph node dissection, the lymphedema risk still exists, and identifying which patients actually benefit from SLNB is critical, he said.

“In our multidisciplinary team, we are working to define selection criteria for postmenopausal patients with HR+HER2- breast cancer who would have met eligibility criteria for the SOUND trial and for whom omission of SLNB would not change adjuvant treatment considerations,” he said.

“Breast surgeons have been moving towards less aggressive axillary surgery based on evidence showing its safety in specific patient cohorts, particularly those with low-risk factors such as older age (70 years and above) and early-stage hormone receptor-positive breast cancer,” Sarah Blair, MD, professor and vice chair in the department of surgery at UC San Diego Health, said in an interview.

“The Choosing Wisely recommendations, issued by the Society of Surgical Oncology, advise against routine use of sentinel lymph node biopsy in women aged 70 and older with early-stage hormone receptor–positive breast cancer; these recommendations are based on clinical trials demonstrating oncologic safety in this population,” said Dr. Blair, who was not involved in the SOUND trial or the current study.

The data from the new study are encouraging and highlight the generalizability of the SOUND results, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said in an interview. The results help to define a low-risk group of patients for which sentinel node staging may be omitted, after multidisciplinary discussion to ensure that nodal staging will not impact adjuvant systemic therapy or radiation decision-making, said Dr. Teshome, who was not involved in the SOUND trial or the current study.
 

What Are the Limitations of the SOUND trial and the New Study?

The current study limitations included its design having been a retrospective review of a prospective database with selection bias, lack of standard criteria for preoperative axillary ultrasound, and the lack of SLNB for many patients older than 70 years based on the Choosing Wisely criteria, Dr. Giannakou said in the press briefing.

“Despite the evidence supporting axillary surgery de-escalation, it can be challenging for surgeons to change their practice based on a single study,” Dr. Blair said an interview. However, the SOUND trial findings support current evidence, giving surgeons more confidence to discuss multidisciplinary treatment options, she said.
 

What Additional Research is Needed?

“Longer follow-up is needed to make definitive conclusions about the oncologic outcomes of axillary surgery de-escalation in this patient population,” said Dr. Blair. “Given that slow-growing tumors are involved, the time to recurrence may extend beyond the typical follow-up period of three years.

“Ongoing research and collaboration among multidisciplinary teams are essential to ensure optimal treatment decisions and patient outcomes,” she emphasized.

Dr. Giannakou, Dr. Blair, and Dr. Teshome had no financial conflicts to disclose.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Using ImPrint, an immune-related biomarker, clinicians can identify patients with breast cancer who are likely to respond to neoadjuvant immunotherapy, according to data from the ongoing phase 2 I-SPY2 trial.

Patient selection based on ImPrint class can result in high response rates and spare nonresponders the toxicities of immunotherapy, said Denise M. Wolf, PhD, during her presentation of the study results at the annual meeting of the American Association for Cancer Research (AACR).

“Our results show that patients with ER+/HER2-/ImPrint+ breast cancer have a very high probability of achieving complete response to immunotherapy, whereas those who are ER+/HER2-/ImPrint- have a low probability of responding,” noted Dr. Wolf, PhD, MSc of the University of California, San Francisco (UCSF), in an interview.

She added that, although effective, immunotherapy also carries the risk of serious immune-related toxicities, and knowledge of ImPrint class can help patients and physicians determine whether immunotherapy is a good treatment option. “Many patients will be willing to take the risk of immunotherapy toxicities if their odds of responding are very high, as is the case for ImPrint+ patients, but [are] likely less enthused with a low likelihood of response,” Dr. Wolf said during the interview.
 

Need for Predictive Biomarkers for Neoadjuvant Immunotherapy

Although neoadjuvant immunotherapy has become the standard treatment for patients with early-stage triple-negative breast cancer (TNBC), chemotherapy remains the mainstay of treatment for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. The I-SPY2 clinical trial is the first randomized clinical study to assess the efficacy of immunotherapy in the high-risk population of patients with HR+/HER2-, Dr. Wolf said. Data from this study suggest that a subset of HR+/HER2- patients may also derive substantial benefit from this approach compared with standard chemotherapy.

“We and others have previously observed that a minority of ER+/HER2- breast cancers are enriched for tumor-infiltrating lymphocytes and that high levels of immune-related gene signatures associate with improved survival in this subtype, as well as in TNBC,” noted Dr. Wolf during an interview.

She explained that patients with high-risk ER+/HER2- breast cancer were not responding to any of the experimental agent classes tested in the trial and showed particularly poor outcomes, and that she and her colleagues “wanted to see if immune-oncology agents would impact response in these patients.”
 

ImPrint, an Immune Expression Signature

Preliminary data from the I-SPY2 trial showed that immune-related gene signatures were associated with pathologic complete response (pCR) in patients with HR+/HER2- breast cancer treated with immunotherapy. This observation allowed investigators to develop a clinically applicable immune classifier, termed ImPrint, to predict response to immunotherapy in this population.

This immune classifier is a 53-gene signature developed using data from the first anti–programmed death-1 (PD-1) arm that included patients treated with pembrolizumab, explained Dr. Wolf.
 

Performance of ImPrint in Patients With HR+/HER2- Breast Cancer

Dr. Wolf presented new data on the performance of ImPrint in 204 patients with high-risk HR+/HER2- breast cancer from the following five immunotherapy arms of the I-SPY2 trial, at the meeting. These arms included: anti–PD-1, anti–PDL-1 plus PARP inhibitor, anti–PD-1/TLR9 dual immunotherapy, and anti–PD-1 with or without LAG3 inhibitor. Data from 191 patients treated with the current standard of care (paclitaxel followed by adriamycin and cyclophosphamide cytoxan) were included in the analysis as a control.

The pCR in the entire population across these five immunotherapy arms was 33%. The response rate in the control arm was 13.5%.

“The high pCR in the immunotherapy groups is remarkable given the traditionally poor response of HR+/HER2- tumors to standard neoadjuvant chemotherapy,” said Ritu Aneja, PhD, the associate dean for research and innovation at the University of Alabama at Birmingham and a breast cancer expert, who was not involved in the I-SPY2 trial.

When patients were stratified according to ImPrint status, significant differences were observed among the groups. In this analysis, 28% of HR+/HER2- patients were classified as ImPrint positive (likely sensitive) based on ImPrint expression levels in pretreatment mRNA samples, and these individuals achieved pCR rates as high as 76% with immunotherapy.

In comparison, pCR rates were only 16% in ImPrint-negative (likely resistant) patients. The highest response rate was observed in the anti–PD-1/TLR9 dual immunotherapy arm, with a pCR rate of greater than 90% in ImPrint-positive patients. In the control arm, pCR rates were 33% in ImPrint-positive and 8% in ImPrint-negative patients.

“These results suggest that a subset of [patients with] high-risk HR+/HER2- breast cancers is highly sensitive to immunotherapy,” said Dr. Aneja in an interview. “By using a specific and sensitive selection strategy like ImPrint, we may be able to identify patients who can achieve pCR rates similar to what we see with the best neoadjuvant therapies in triple-negative and HER2-positive disease.”
 

Ability of ImPrint to Predict Long-Term Outcomes

During her talk, Dr. Wolf explained that she and her research team currently do not have sufficient follow-up data to assess the ability of ImPrint to predict long-term outcomes. Therefore, they used the pCR data to predict long-term disease-free survival (DRFS) outcomes. Based on their model, HR+/HER2-/ImPrint+ patients treated with immunotherapy were estimated to have a 91% 5-year DRFS rate, compared with 80% for those receiving standard chemotherapy alone. This represents a 52% reduction in the risk of disease recurrence.

“This suggests not only a higher immediate response rate to therapy but also potential long-term benefits for patients identified as ImPrint+,” Dr. Aneja said, commenting on the significance of the DRFS data, during the interview, She added that the ability to predict longer-term outcomes is a critical advantage in selecting the most effective treatment strategies for patients.
 

Comparison of ImPrint With Other Biomarkers

The investigators compared ImPrint to other potential biomarkers for immunotherapy response, including MammaPrint (ultra) High2 risk (MP2) and tumor grade. During her talk, Dr. Wolf showed data demonstrating that ImPrint is a more precise predictor of pCR, with higher response rates than either of those other markers.

The pCR rates for MP2 and grade III were 56% and 45%, respectively, which are much smaller than the pCR rates observed for ImPrint+ patients (75%).

“This difference underscores ImPrint’s effectiveness in distinguishing patients who could benefit from immunotherapy, offering a pCR prediction accuracy that is significantly higher than seen with other biomarkers that have been proposed as selection markers for neoadjuvant immunotherapy trials in HR+/HER2- breast cancers, such as MP2 and tumor grade,” said Dr. Aneja, during the interview.
 

Looking Ahead — Implementation of Imprint for Patient Selection

Dr. Aneja echoed that the findings from the I-SPY2 trial advocate for the integration of biomarker-driven approaches, particularly the use of the ImPrint classifier, into the treatment planning process for high-risk HR+/HER2- breast cancer.

“This approach can enable clinicians to identify patients who are more likely to benefit from immunotherapy, thus personalizing treatment strategies and potentially enhancing treatment efficacy while minimizing exposure to unnecessary toxicity for those unlikely to respond,” she said.

Dr. Aneja added that while the I-SPY2 trial offers promising data on ImPrint’s efficacy, additional prospective studies are needed to validate these findings across diverse patient populations and settings, as well as the correlation between biomarker positivity and long-term clinical outcomes, including DRFS and overall survival. “This will help to better understand the full spectrum of benefits provided by immunotherapies in biomarker-selected patient groups,” she said.

Dr. Wolf and Dr. Aneja reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Using ImPrint, an immune-related biomarker, clinicians can identify patients with breast cancer who are likely to respond to neoadjuvant immunotherapy, according to data from the ongoing phase 2 I-SPY2 trial.

Patient selection based on ImPrint class can result in high response rates and spare nonresponders the toxicities of immunotherapy, said Denise M. Wolf, PhD, during her presentation of the study results at the annual meeting of the American Association for Cancer Research (AACR).

“Our results show that patients with ER+/HER2-/ImPrint+ breast cancer have a very high probability of achieving complete response to immunotherapy, whereas those who are ER+/HER2-/ImPrint- have a low probability of responding,” noted Dr. Wolf, PhD, MSc of the University of California, San Francisco (UCSF), in an interview.

She added that, although effective, immunotherapy also carries the risk of serious immune-related toxicities, and knowledge of ImPrint class can help patients and physicians determine whether immunotherapy is a good treatment option. “Many patients will be willing to take the risk of immunotherapy toxicities if their odds of responding are very high, as is the case for ImPrint+ patients, but [are] likely less enthused with a low likelihood of response,” Dr. Wolf said during the interview.
 

Need for Predictive Biomarkers for Neoadjuvant Immunotherapy

Although neoadjuvant immunotherapy has become the standard treatment for patients with early-stage triple-negative breast cancer (TNBC), chemotherapy remains the mainstay of treatment for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. The I-SPY2 clinical trial is the first randomized clinical study to assess the efficacy of immunotherapy in the high-risk population of patients with HR+/HER2-, Dr. Wolf said. Data from this study suggest that a subset of HR+/HER2- patients may also derive substantial benefit from this approach compared with standard chemotherapy.

“We and others have previously observed that a minority of ER+/HER2- breast cancers are enriched for tumor-infiltrating lymphocytes and that high levels of immune-related gene signatures associate with improved survival in this subtype, as well as in TNBC,” noted Dr. Wolf during an interview.

She explained that patients with high-risk ER+/HER2- breast cancer were not responding to any of the experimental agent classes tested in the trial and showed particularly poor outcomes, and that she and her colleagues “wanted to see if immune-oncology agents would impact response in these patients.”
 

ImPrint, an Immune Expression Signature

Preliminary data from the I-SPY2 trial showed that immune-related gene signatures were associated with pathologic complete response (pCR) in patients with HR+/HER2- breast cancer treated with immunotherapy. This observation allowed investigators to develop a clinically applicable immune classifier, termed ImPrint, to predict response to immunotherapy in this population.

This immune classifier is a 53-gene signature developed using data from the first anti–programmed death-1 (PD-1) arm that included patients treated with pembrolizumab, explained Dr. Wolf.
 

Performance of ImPrint in Patients With HR+/HER2- Breast Cancer

Dr. Wolf presented new data on the performance of ImPrint in 204 patients with high-risk HR+/HER2- breast cancer from the following five immunotherapy arms of the I-SPY2 trial, at the meeting. These arms included: anti–PD-1, anti–PDL-1 plus PARP inhibitor, anti–PD-1/TLR9 dual immunotherapy, and anti–PD-1 with or without LAG3 inhibitor. Data from 191 patients treated with the current standard of care (paclitaxel followed by adriamycin and cyclophosphamide cytoxan) were included in the analysis as a control.

The pCR in the entire population across these five immunotherapy arms was 33%. The response rate in the control arm was 13.5%.

“The high pCR in the immunotherapy groups is remarkable given the traditionally poor response of HR+/HER2- tumors to standard neoadjuvant chemotherapy,” said Ritu Aneja, PhD, the associate dean for research and innovation at the University of Alabama at Birmingham and a breast cancer expert, who was not involved in the I-SPY2 trial.

When patients were stratified according to ImPrint status, significant differences were observed among the groups. In this analysis, 28% of HR+/HER2- patients were classified as ImPrint positive (likely sensitive) based on ImPrint expression levels in pretreatment mRNA samples, and these individuals achieved pCR rates as high as 76% with immunotherapy.

In comparison, pCR rates were only 16% in ImPrint-negative (likely resistant) patients. The highest response rate was observed in the anti–PD-1/TLR9 dual immunotherapy arm, with a pCR rate of greater than 90% in ImPrint-positive patients. In the control arm, pCR rates were 33% in ImPrint-positive and 8% in ImPrint-negative patients.

“These results suggest that a subset of [patients with] high-risk HR+/HER2- breast cancers is highly sensitive to immunotherapy,” said Dr. Aneja in an interview. “By using a specific and sensitive selection strategy like ImPrint, we may be able to identify patients who can achieve pCR rates similar to what we see with the best neoadjuvant therapies in triple-negative and HER2-positive disease.”
 

Ability of ImPrint to Predict Long-Term Outcomes

During her talk, Dr. Wolf explained that she and her research team currently do not have sufficient follow-up data to assess the ability of ImPrint to predict long-term outcomes. Therefore, they used the pCR data to predict long-term disease-free survival (DRFS) outcomes. Based on their model, HR+/HER2-/ImPrint+ patients treated with immunotherapy were estimated to have a 91% 5-year DRFS rate, compared with 80% for those receiving standard chemotherapy alone. This represents a 52% reduction in the risk of disease recurrence.

“This suggests not only a higher immediate response rate to therapy but also potential long-term benefits for patients identified as ImPrint+,” Dr. Aneja said, commenting on the significance of the DRFS data, during the interview, She added that the ability to predict longer-term outcomes is a critical advantage in selecting the most effective treatment strategies for patients.
 

Comparison of ImPrint With Other Biomarkers

The investigators compared ImPrint to other potential biomarkers for immunotherapy response, including MammaPrint (ultra) High2 risk (MP2) and tumor grade. During her talk, Dr. Wolf showed data demonstrating that ImPrint is a more precise predictor of pCR, with higher response rates than either of those other markers.

The pCR rates for MP2 and grade III were 56% and 45%, respectively, which are much smaller than the pCR rates observed for ImPrint+ patients (75%).

“This difference underscores ImPrint’s effectiveness in distinguishing patients who could benefit from immunotherapy, offering a pCR prediction accuracy that is significantly higher than seen with other biomarkers that have been proposed as selection markers for neoadjuvant immunotherapy trials in HR+/HER2- breast cancers, such as MP2 and tumor grade,” said Dr. Aneja, during the interview.
 

Looking Ahead — Implementation of Imprint for Patient Selection

Dr. Aneja echoed that the findings from the I-SPY2 trial advocate for the integration of biomarker-driven approaches, particularly the use of the ImPrint classifier, into the treatment planning process for high-risk HR+/HER2- breast cancer.

“This approach can enable clinicians to identify patients who are more likely to benefit from immunotherapy, thus personalizing treatment strategies and potentially enhancing treatment efficacy while minimizing exposure to unnecessary toxicity for those unlikely to respond,” she said.

Dr. Aneja added that while the I-SPY2 trial offers promising data on ImPrint’s efficacy, additional prospective studies are needed to validate these findings across diverse patient populations and settings, as well as the correlation between biomarker positivity and long-term clinical outcomes, including DRFS and overall survival. “This will help to better understand the full spectrum of benefits provided by immunotherapies in biomarker-selected patient groups,” she said.

Dr. Wolf and Dr. Aneja reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Using ImPrint, an immune-related biomarker, clinicians can identify patients with breast cancer who are likely to respond to neoadjuvant immunotherapy, according to data from the ongoing phase 2 I-SPY2 trial.

Patient selection based on ImPrint class can result in high response rates and spare nonresponders the toxicities of immunotherapy, said Denise M. Wolf, PhD, during her presentation of the study results at the annual meeting of the American Association for Cancer Research (AACR).

“Our results show that patients with ER+/HER2-/ImPrint+ breast cancer have a very high probability of achieving complete response to immunotherapy, whereas those who are ER+/HER2-/ImPrint- have a low probability of responding,” noted Dr. Wolf, PhD, MSc of the University of California, San Francisco (UCSF), in an interview.

She added that, although effective, immunotherapy also carries the risk of serious immune-related toxicities, and knowledge of ImPrint class can help patients and physicians determine whether immunotherapy is a good treatment option. “Many patients will be willing to take the risk of immunotherapy toxicities if their odds of responding are very high, as is the case for ImPrint+ patients, but [are] likely less enthused with a low likelihood of response,” Dr. Wolf said during the interview.
 

Need for Predictive Biomarkers for Neoadjuvant Immunotherapy

Although neoadjuvant immunotherapy has become the standard treatment for patients with early-stage triple-negative breast cancer (TNBC), chemotherapy remains the mainstay of treatment for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. The I-SPY2 clinical trial is the first randomized clinical study to assess the efficacy of immunotherapy in the high-risk population of patients with HR+/HER2-, Dr. Wolf said. Data from this study suggest that a subset of HR+/HER2- patients may also derive substantial benefit from this approach compared with standard chemotherapy.

“We and others have previously observed that a minority of ER+/HER2- breast cancers are enriched for tumor-infiltrating lymphocytes and that high levels of immune-related gene signatures associate with improved survival in this subtype, as well as in TNBC,” noted Dr. Wolf during an interview.

She explained that patients with high-risk ER+/HER2- breast cancer were not responding to any of the experimental agent classes tested in the trial and showed particularly poor outcomes, and that she and her colleagues “wanted to see if immune-oncology agents would impact response in these patients.”
 

ImPrint, an Immune Expression Signature

Preliminary data from the I-SPY2 trial showed that immune-related gene signatures were associated with pathologic complete response (pCR) in patients with HR+/HER2- breast cancer treated with immunotherapy. This observation allowed investigators to develop a clinically applicable immune classifier, termed ImPrint, to predict response to immunotherapy in this population.

This immune classifier is a 53-gene signature developed using data from the first anti–programmed death-1 (PD-1) arm that included patients treated with pembrolizumab, explained Dr. Wolf.
 

Performance of ImPrint in Patients With HR+/HER2- Breast Cancer

Dr. Wolf presented new data on the performance of ImPrint in 204 patients with high-risk HR+/HER2- breast cancer from the following five immunotherapy arms of the I-SPY2 trial, at the meeting. These arms included: anti–PD-1, anti–PDL-1 plus PARP inhibitor, anti–PD-1/TLR9 dual immunotherapy, and anti–PD-1 with or without LAG3 inhibitor. Data from 191 patients treated with the current standard of care (paclitaxel followed by adriamycin and cyclophosphamide cytoxan) were included in the analysis as a control.

The pCR in the entire population across these five immunotherapy arms was 33%. The response rate in the control arm was 13.5%.

“The high pCR in the immunotherapy groups is remarkable given the traditionally poor response of HR+/HER2- tumors to standard neoadjuvant chemotherapy,” said Ritu Aneja, PhD, the associate dean for research and innovation at the University of Alabama at Birmingham and a breast cancer expert, who was not involved in the I-SPY2 trial.

When patients were stratified according to ImPrint status, significant differences were observed among the groups. In this analysis, 28% of HR+/HER2- patients were classified as ImPrint positive (likely sensitive) based on ImPrint expression levels in pretreatment mRNA samples, and these individuals achieved pCR rates as high as 76% with immunotherapy.

In comparison, pCR rates were only 16% in ImPrint-negative (likely resistant) patients. The highest response rate was observed in the anti–PD-1/TLR9 dual immunotherapy arm, with a pCR rate of greater than 90% in ImPrint-positive patients. In the control arm, pCR rates were 33% in ImPrint-positive and 8% in ImPrint-negative patients.

“These results suggest that a subset of [patients with] high-risk HR+/HER2- breast cancers is highly sensitive to immunotherapy,” said Dr. Aneja in an interview. “By using a specific and sensitive selection strategy like ImPrint, we may be able to identify patients who can achieve pCR rates similar to what we see with the best neoadjuvant therapies in triple-negative and HER2-positive disease.”
 

Ability of ImPrint to Predict Long-Term Outcomes

During her talk, Dr. Wolf explained that she and her research team currently do not have sufficient follow-up data to assess the ability of ImPrint to predict long-term outcomes. Therefore, they used the pCR data to predict long-term disease-free survival (DRFS) outcomes. Based on their model, HR+/HER2-/ImPrint+ patients treated with immunotherapy were estimated to have a 91% 5-year DRFS rate, compared with 80% for those receiving standard chemotherapy alone. This represents a 52% reduction in the risk of disease recurrence.

“This suggests not only a higher immediate response rate to therapy but also potential long-term benefits for patients identified as ImPrint+,” Dr. Aneja said, commenting on the significance of the DRFS data, during the interview, She added that the ability to predict longer-term outcomes is a critical advantage in selecting the most effective treatment strategies for patients.
 

Comparison of ImPrint With Other Biomarkers

The investigators compared ImPrint to other potential biomarkers for immunotherapy response, including MammaPrint (ultra) High2 risk (MP2) and tumor grade. During her talk, Dr. Wolf showed data demonstrating that ImPrint is a more precise predictor of pCR, with higher response rates than either of those other markers.

The pCR rates for MP2 and grade III were 56% and 45%, respectively, which are much smaller than the pCR rates observed for ImPrint+ patients (75%).

“This difference underscores ImPrint’s effectiveness in distinguishing patients who could benefit from immunotherapy, offering a pCR prediction accuracy that is significantly higher than seen with other biomarkers that have been proposed as selection markers for neoadjuvant immunotherapy trials in HR+/HER2- breast cancers, such as MP2 and tumor grade,” said Dr. Aneja, during the interview.
 

Looking Ahead — Implementation of Imprint for Patient Selection

Dr. Aneja echoed that the findings from the I-SPY2 trial advocate for the integration of biomarker-driven approaches, particularly the use of the ImPrint classifier, into the treatment planning process for high-risk HR+/HER2- breast cancer.

“This approach can enable clinicians to identify patients who are more likely to benefit from immunotherapy, thus personalizing treatment strategies and potentially enhancing treatment efficacy while minimizing exposure to unnecessary toxicity for those unlikely to respond,” she said.

Dr. Aneja added that while the I-SPY2 trial offers promising data on ImPrint’s efficacy, additional prospective studies are needed to validate these findings across diverse patient populations and settings, as well as the correlation between biomarker positivity and long-term clinical outcomes, including DRFS and overall survival. “This will help to better understand the full spectrum of benefits provided by immunotherapies in biomarker-selected patient groups,” she said.

Dr. Wolf and Dr. Aneja reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the approval of fam-trastuzumab–deruxtecan-nxki (Enhertu; AstraZeneca and Daiichi Sankyo, Inc) to adults with unresectable or metastatic HER2-positive solid tumors who have no satisfactory alternative after prior systemic treatment.

The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.

The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.

“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”

Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.

Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.

The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.

Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity. 

The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the approval of fam-trastuzumab–deruxtecan-nxki (Enhertu; AstraZeneca and Daiichi Sankyo, Inc) to adults with unresectable or metastatic HER2-positive solid tumors who have no satisfactory alternative after prior systemic treatment.

The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.

The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.

“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”

Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.

Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.

The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.

Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity. 

The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the approval of fam-trastuzumab–deruxtecan-nxki (Enhertu; AstraZeneca and Daiichi Sankyo, Inc) to adults with unresectable or metastatic HER2-positive solid tumors who have no satisfactory alternative after prior systemic treatment.

The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.

The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.

“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”

Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.

Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.

The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.

Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity. 

The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
 

A version of this article appeared on Medscape.com.

High levels of tumor-infiltrating lymphocytes predicted increased survival in patients with early-stage triple-negative breast cancer who did not receive chemotherapy, a new analysis finds.

The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.

Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.

“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”

  

What is Known About Tumor-Infiltrating Lymphocytes and Cancer?

Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.

Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.

The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview. 

The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.

“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.

 

What Does the New Study Add?

The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.

The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.

A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.

Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.

The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.

“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
 

What are the Limitations of This Research?

The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.

“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.

To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.

“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.

What Do Oncologists Need to Know?

The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.

“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”

In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.

Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.

What Additional Research is Needed?

Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.

“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.

The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.

High levels of tumor-infiltrating lymphocytes predicted increased survival in patients with early-stage triple-negative breast cancer who did not receive chemotherapy, a new analysis finds.

The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.

Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.

“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”

  

What is Known About Tumor-Infiltrating Lymphocytes and Cancer?

Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.

Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.

The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview. 

The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.

“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.

 

What Does the New Study Add?

The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.

The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.

A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.

Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.

The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.

“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
 

What are the Limitations of This Research?

The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.

“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.

To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.

“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.

What Do Oncologists Need to Know?

The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.

“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”

In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.

Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.

What Additional Research is Needed?

Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.

“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.

The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.

High levels of tumor-infiltrating lymphocytes predicted increased survival in patients with early-stage triple-negative breast cancer who did not receive chemotherapy, a new analysis finds.

The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.

Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.

“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”

  

What is Known About Tumor-Infiltrating Lymphocytes and Cancer?

Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.

Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.

The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview. 

The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.

“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.

 

What Does the New Study Add?

The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.

The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.

A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.

Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.

The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.

“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
 

What are the Limitations of This Research?

The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.

“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.

To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.

“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.

What Do Oncologists Need to Know?

The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.

“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”

In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.

Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.

What Additional Research is Needed?

Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.

“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.

The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.