Breast Cancer

Key clinical point: Circulating tumor cell (CTC) count-driven first-line therapy (chemotherapy or endocrine therapy) is noninferior to clinician choice-driven first-line therapy for progression-free survival (PFS) in hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.

Major finding: The median PFS was 15.5 (95% confidence interval [CI], 12.7-17.3) months in the CTC-guided group and 13.9 (95% CI, 12.2-16.3) months in the clinician-driven choice group. The primary end point (PFS in the per-protocol population with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio [HR]) was met with an HR of 0.94 (90% CI, 0.81-1.09). Overall survival was also noninferior with CTC guidance (HR, 0.91; 95% CI, 0.71-1.16).

Study details: In this phase 3 STIC CTC trial, 755 women with HR-positive/HER2-negative metastatic breast cancer were randomly assigned (1:1) to receive a CTC-driven first-line therapy (chemotherapy if 5 CTCs or more/7.5 mL; endocrine therapy if less than 5 CTCs/7.5 mL) or clinician choice-driven first-line therapy (chemotherapy or endocrine therapy) at 17 French centers.

Disclosures: The study was funded by Institut Curie, the French National Cancer Institute as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011, and Menarini Silicon Biosystems. The lead author reported receiving grants and nonfinancial support from Menarini Silicon Biosystems during the conduct of the study.

Source: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.

Key clinical point: Circulating tumor cell (CTC) count-driven first-line therapy (chemotherapy or endocrine therapy) is noninferior to clinician choice-driven first-line therapy for progression-free survival (PFS) in hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.

Major finding: The median PFS was 15.5 (95% confidence interval [CI], 12.7-17.3) months in the CTC-guided group and 13.9 (95% CI, 12.2-16.3) months in the clinician-driven choice group. The primary end point (PFS in the per-protocol population with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio [HR]) was met with an HR of 0.94 (90% CI, 0.81-1.09). Overall survival was also noninferior with CTC guidance (HR, 0.91; 95% CI, 0.71-1.16).

Study details: In this phase 3 STIC CTC trial, 755 women with HR-positive/HER2-negative metastatic breast cancer were randomly assigned (1:1) to receive a CTC-driven first-line therapy (chemotherapy if 5 CTCs or more/7.5 mL; endocrine therapy if less than 5 CTCs/7.5 mL) or clinician choice-driven first-line therapy (chemotherapy or endocrine therapy) at 17 French centers.

Disclosures: The study was funded by Institut Curie, the French National Cancer Institute as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011, and Menarini Silicon Biosystems. The lead author reported receiving grants and nonfinancial support from Menarini Silicon Biosystems during the conduct of the study.

Source: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.

Key clinical point: Circulating tumor cell (CTC) count-driven first-line therapy (chemotherapy or endocrine therapy) is noninferior to clinician choice-driven first-line therapy for progression-free survival (PFS) in hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.

Major finding: The median PFS was 15.5 (95% confidence interval [CI], 12.7-17.3) months in the CTC-guided group and 13.9 (95% CI, 12.2-16.3) months in the clinician-driven choice group. The primary end point (PFS in the per-protocol population with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio [HR]) was met with an HR of 0.94 (90% CI, 0.81-1.09). Overall survival was also noninferior with CTC guidance (HR, 0.91; 95% CI, 0.71-1.16).

Study details: In this phase 3 STIC CTC trial, 755 women with HR-positive/HER2-negative metastatic breast cancer were randomly assigned (1:1) to receive a CTC-driven first-line therapy (chemotherapy if 5 CTCs or more/7.5 mL; endocrine therapy if less than 5 CTCs/7.5 mL) or clinician choice-driven first-line therapy (chemotherapy or endocrine therapy) at 17 French centers.

Disclosures: The study was funded by Institut Curie, the French National Cancer Institute as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011, and Menarini Silicon Biosystems. The lead author reported receiving grants and nonfinancial support from Menarini Silicon Biosystems during the conduct of the study.

Source: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.

Key clinical point: Addition of ipatasertib to paclitaxel does not improve progression-free survival (PFS) in patients with PIK3CA/AKT1/PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer (TNBC).

Major finding: The median PFS was 7.4 months with ipatasertib + paclitaxel vs 6.1 months with placebo + paclitaxel (hazard ratio, 1.02; P = .9237).

Study details: The data come from the Cohort A of phase 3 trial IPATunity130. 255 patients with PIK3CA/AKT1/PTEN-altered TNBC were randomly assigned (2:1) to receive paclitaxel with either ipatasertib or placebo.

Disclosures: The study was funded by Hoffmann-La Roche. The presenting author Rebecca Dent declared relationships with AstraZeneca, Eisai, Lilly, Merck, Novartis, Pfizer, and Roche.

Source: Dent R et al. Abstract 4. SABCS 2020. 2020 Dec 10.

Key clinical point: Addition of ipatasertib to paclitaxel does not improve progression-free survival (PFS) in patients with PIK3CA/AKT1/PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer (TNBC).

Major finding: The median PFS was 7.4 months with ipatasertib + paclitaxel vs 6.1 months with placebo + paclitaxel (hazard ratio, 1.02; P = .9237).

Study details: The data come from the Cohort A of phase 3 trial IPATunity130. 255 patients with PIK3CA/AKT1/PTEN-altered TNBC were randomly assigned (2:1) to receive paclitaxel with either ipatasertib or placebo.

Disclosures: The study was funded by Hoffmann-La Roche. The presenting author Rebecca Dent declared relationships with AstraZeneca, Eisai, Lilly, Merck, Novartis, Pfizer, and Roche.

Source: Dent R et al. Abstract 4. SABCS 2020. 2020 Dec 10.

Key clinical point: Addition of ipatasertib to paclitaxel does not improve progression-free survival (PFS) in patients with PIK3CA/AKT1/PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer (TNBC).

Major finding: The median PFS was 7.4 months with ipatasertib + paclitaxel vs 6.1 months with placebo + paclitaxel (hazard ratio, 1.02; P = .9237).

Study details: The data come from the Cohort A of phase 3 trial IPATunity130. 255 patients with PIK3CA/AKT1/PTEN-altered TNBC were randomly assigned (2:1) to receive paclitaxel with either ipatasertib or placebo.

Disclosures: The study was funded by Hoffmann-La Roche. The presenting author Rebecca Dent declared relationships with AstraZeneca, Eisai, Lilly, Merck, Novartis, Pfizer, and Roche.

Source: Dent R et al. Abstract 4. SABCS 2020. 2020 Dec 10.

The majority of women in the United States remain unaware of the benefits breastfeeding offers in reducing the risk of breast cancer, reported Adrienne Hoyt-Austin, DO, and colleagues at University of California, Davis.

oksun70/ThinkStock

Using nationally representative data collected from the 2015-2017 National Survey of Family Growth, Dr. Hoyt-Austin and colleagues analyzed responses to the question: “Do you think that breastfeeding decreases a woman’s chances of getting breast cancer a lot, a little, or not at all, no opinion, or don’t know?” A total of 5,554 female respondents aged 15-49 years participated. The response rate was 66.7%.
 

Multiparous status and education play a role in decreased awareness

Those who had given birth more than once, who had no more than a high school education, or who were U.S.-born Hispanic had the lowest level of awareness, believing that breastfeeding offers only “a little” protection. Of those who were aware of the link, 44% reported that breastfeeding provides “a lot” of protection, and foreign-born participants as well as those who breastfed for more than a year were more likely to conclude that breastfeeding offers “a lot” of protection. The researchers found that neither mammogram or personal family history of breast cancer had any bearing on awareness.

Although multiple studies have found breastfeeding to confer a lower rate of cancer risk, morbidity and mortality, with a 26% lower lifetime risk for those mothers who breastfeed for 12 months or longer, only 36% of women in the United States actually breastfeed.
 

Limited data indicate whether respondents were breastfed themselves

“Public health initiatives must consider the complex roots of disparities in breastfeeding,” noted Dr. Hoyt-Austin and colleagues. They acknowledged the subjectivity of perceptions of “a lot” versus “a little” and noted that the study was limited by a lack of data on whether participants were breastfed themselves.

Clinicians have an opportunity to play a key role in better educating families concerning the benefits of breastfeeding, both for mother and child, they advised. According to one recent study, just 5 minutes of counseling on the benefits of breastfeeding “significantly strengthened women’s intentions to breastfeed.

In a separate interview, Amy E. Cyr, MD, FACS, section of surgical oncology at Washington University, St. Louis, noted that “many breast cancer risk factors – age, sex, family history, and age of menopause – are nonmodifiable.” And while other risk factors, including alcohol use, diet, and exercise are controllable, “pregnancies and breastfeeding don’t always go as planned,” Dr. Cyr added.

“Although Dr. Hoyt-Austin et al. observed that many women aren’t aware that breastfeeding decreases breast cancer risk – or to what extent (they cite a 26% cancer risk reduction after 12 or more months of breastfeeding) – most studies haven’t shown that large a drop in breast cancer risk,“ she pointed out, adding that “I think it’s an overstatement to suggest that breastfeeding reduces cancer risk by ‘a lot,’ as one of the survey choices offered in the study suggests.”

Whether or not a woman breastfeeds depends not only on desire but on social and economic support and biology; for some, breastfeeding simply isn’t an option. “I agree that we should educate women about the benefits of breastfeeding so they can make an informed decision for themselves and their infants, but we also need to acknowledge the complexity of this issue,” she cautioned.

One coauthor reported a travel stipend by the Human Milk Banking Association of North America; Dr. Hoyt-Austin and the other authors had no conflicts of interest to report. Dr. Cyr had no conflicts of interest to report.

SOURCE: Hoyt-Austin A et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004162.

The majority of women in the United States remain unaware of the benefits breastfeeding offers in reducing the risk of breast cancer, reported Adrienne Hoyt-Austin, DO, and colleagues at University of California, Davis.

oksun70/ThinkStock

Using nationally representative data collected from the 2015-2017 National Survey of Family Growth, Dr. Hoyt-Austin and colleagues analyzed responses to the question: “Do you think that breastfeeding decreases a woman’s chances of getting breast cancer a lot, a little, or not at all, no opinion, or don’t know?” A total of 5,554 female respondents aged 15-49 years participated. The response rate was 66.7%.
 

Multiparous status and education play a role in decreased awareness

Those who had given birth more than once, who had no more than a high school education, or who were U.S.-born Hispanic had the lowest level of awareness, believing that breastfeeding offers only “a little” protection. Of those who were aware of the link, 44% reported that breastfeeding provides “a lot” of protection, and foreign-born participants as well as those who breastfed for more than a year were more likely to conclude that breastfeeding offers “a lot” of protection. The researchers found that neither mammogram or personal family history of breast cancer had any bearing on awareness.

Although multiple studies have found breastfeeding to confer a lower rate of cancer risk, morbidity and mortality, with a 26% lower lifetime risk for those mothers who breastfeed for 12 months or longer, only 36% of women in the United States actually breastfeed.
 

Limited data indicate whether respondents were breastfed themselves

“Public health initiatives must consider the complex roots of disparities in breastfeeding,” noted Dr. Hoyt-Austin and colleagues. They acknowledged the subjectivity of perceptions of “a lot” versus “a little” and noted that the study was limited by a lack of data on whether participants were breastfed themselves.

Clinicians have an opportunity to play a key role in better educating families concerning the benefits of breastfeeding, both for mother and child, they advised. According to one recent study, just 5 minutes of counseling on the benefits of breastfeeding “significantly strengthened women’s intentions to breastfeed.

In a separate interview, Amy E. Cyr, MD, FACS, section of surgical oncology at Washington University, St. Louis, noted that “many breast cancer risk factors – age, sex, family history, and age of menopause – are nonmodifiable.” And while other risk factors, including alcohol use, diet, and exercise are controllable, “pregnancies and breastfeeding don’t always go as planned,” Dr. Cyr added.

“Although Dr. Hoyt-Austin et al. observed that many women aren’t aware that breastfeeding decreases breast cancer risk – or to what extent (they cite a 26% cancer risk reduction after 12 or more months of breastfeeding) – most studies haven’t shown that large a drop in breast cancer risk,“ she pointed out, adding that “I think it’s an overstatement to suggest that breastfeeding reduces cancer risk by ‘a lot,’ as one of the survey choices offered in the study suggests.”

Whether or not a woman breastfeeds depends not only on desire but on social and economic support and biology; for some, breastfeeding simply isn’t an option. “I agree that we should educate women about the benefits of breastfeeding so they can make an informed decision for themselves and their infants, but we also need to acknowledge the complexity of this issue,” she cautioned.

One coauthor reported a travel stipend by the Human Milk Banking Association of North America; Dr. Hoyt-Austin and the other authors had no conflicts of interest to report. Dr. Cyr had no conflicts of interest to report.

SOURCE: Hoyt-Austin A et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004162.

The majority of women in the United States remain unaware of the benefits breastfeeding offers in reducing the risk of breast cancer, reported Adrienne Hoyt-Austin, DO, and colleagues at University of California, Davis.

oksun70/ThinkStock

Using nationally representative data collected from the 2015-2017 National Survey of Family Growth, Dr. Hoyt-Austin and colleagues analyzed responses to the question: “Do you think that breastfeeding decreases a woman’s chances of getting breast cancer a lot, a little, or not at all, no opinion, or don’t know?” A total of 5,554 female respondents aged 15-49 years participated. The response rate was 66.7%.
 

Multiparous status and education play a role in decreased awareness

Those who had given birth more than once, who had no more than a high school education, or who were U.S.-born Hispanic had the lowest level of awareness, believing that breastfeeding offers only “a little” protection. Of those who were aware of the link, 44% reported that breastfeeding provides “a lot” of protection, and foreign-born participants as well as those who breastfed for more than a year were more likely to conclude that breastfeeding offers “a lot” of protection. The researchers found that neither mammogram or personal family history of breast cancer had any bearing on awareness.

Although multiple studies have found breastfeeding to confer a lower rate of cancer risk, morbidity and mortality, with a 26% lower lifetime risk for those mothers who breastfeed for 12 months or longer, only 36% of women in the United States actually breastfeed.
 

Limited data indicate whether respondents were breastfed themselves

“Public health initiatives must consider the complex roots of disparities in breastfeeding,” noted Dr. Hoyt-Austin and colleagues. They acknowledged the subjectivity of perceptions of “a lot” versus “a little” and noted that the study was limited by a lack of data on whether participants were breastfed themselves.

Clinicians have an opportunity to play a key role in better educating families concerning the benefits of breastfeeding, both for mother and child, they advised. According to one recent study, just 5 minutes of counseling on the benefits of breastfeeding “significantly strengthened women’s intentions to breastfeed.

In a separate interview, Amy E. Cyr, MD, FACS, section of surgical oncology at Washington University, St. Louis, noted that “many breast cancer risk factors – age, sex, family history, and age of menopause – are nonmodifiable.” And while other risk factors, including alcohol use, diet, and exercise are controllable, “pregnancies and breastfeeding don’t always go as planned,” Dr. Cyr added.

“Although Dr. Hoyt-Austin et al. observed that many women aren’t aware that breastfeeding decreases breast cancer risk – or to what extent (they cite a 26% cancer risk reduction after 12 or more months of breastfeeding) – most studies haven’t shown that large a drop in breast cancer risk,“ she pointed out, adding that “I think it’s an overstatement to suggest that breastfeeding reduces cancer risk by ‘a lot,’ as one of the survey choices offered in the study suggests.”

Whether or not a woman breastfeeds depends not only on desire but on social and economic support and biology; for some, breastfeeding simply isn’t an option. “I agree that we should educate women about the benefits of breastfeeding so they can make an informed decision for themselves and their infants, but we also need to acknowledge the complexity of this issue,” she cautioned.

One coauthor reported a travel stipend by the Human Milk Banking Association of North America; Dr. Hoyt-Austin and the other authors had no conflicts of interest to report. Dr. Cyr had no conflicts of interest to report.

SOURCE: Hoyt-Austin A et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004162.

Dr. Sara Hurvitz, Director of the Breast Cancer Clinical Trials Program at UCLA, reviews key updates in HER2-positive metastatic breast cancer studies presented during the 2020 San Antonio Breast Cancer Symposium (SABCS), which was held virtually in December.

A sub-analysis of patients who had central nervous system disease at baseline demonstrated improved outcomes with neratinib plus capecitabine compared with those receiving lapatinib plus capecitabine in the NALA trial.

Updated results from the DESTINY-breast01 study of trastuzumab deruxtecan show encouraging results in progression-free survival and early overall survival and high rates of durable responses in a heavily pretreated group of patients with metastatic breast cancer, consistent with early results.

In the HER2CLIMB study, patients treated with tucatinib in combination with trastuzumab and capecitabine had clinically meaningful improvement in progression-free survival, overall survival, and objective response rate independent of HR status compared with placebo, and patients with HR+ and HR- breast cancer with brain metastases experienced similar benefits.

--

Sara A. Hurvitz, MD, FACP, Professor of Medicine. Director, Breast Cancer Clinical Trials Program, Division of Hematology-Oncology David Geffen School of Medicine at UCLA
Medical Director, Clinical Research Unit, UCLA Jonsson Comprehensive Cancer Center.

Dr. Hurvitz has received research grants from: Ambrx; Amgen Inc.; Bayer HealthCare Pharmaceuticals; Daiichi Sankyo, Inc.; Dignitana AB; Eli Lilly and Company; Genentech, Inc.; GlaxoSmithKline; Immunomedics; MacroGenics, Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer Inc; Pieris Pharmaceuticals Inc; Puma Biotechnology; Radius Health; Roche Pharma; sanofi-aventis; Seattle Genetics, Inc.

Dr. Sara Hurvitz, Director of the Breast Cancer Clinical Trials Program at UCLA, reviews key updates in HER2-positive metastatic breast cancer studies presented during the 2020 San Antonio Breast Cancer Symposium (SABCS), which was held virtually in December.

A sub-analysis of patients who had central nervous system disease at baseline demonstrated improved outcomes with neratinib plus capecitabine compared with those receiving lapatinib plus capecitabine in the NALA trial.

Updated results from the DESTINY-breast01 study of trastuzumab deruxtecan show encouraging results in progression-free survival and early overall survival and high rates of durable responses in a heavily pretreated group of patients with metastatic breast cancer, consistent with early results.

In the HER2CLIMB study, patients treated with tucatinib in combination with trastuzumab and capecitabine had clinically meaningful improvement in progression-free survival, overall survival, and objective response rate independent of HR status compared with placebo, and patients with HR+ and HR- breast cancer with brain metastases experienced similar benefits.

--

Sara A. Hurvitz, MD, FACP, Professor of Medicine. Director, Breast Cancer Clinical Trials Program, Division of Hematology-Oncology David Geffen School of Medicine at UCLA
Medical Director, Clinical Research Unit, UCLA Jonsson Comprehensive Cancer Center.

Dr. Hurvitz has received research grants from: Ambrx; Amgen Inc.; Bayer HealthCare Pharmaceuticals; Daiichi Sankyo, Inc.; Dignitana AB; Eli Lilly and Company; Genentech, Inc.; GlaxoSmithKline; Immunomedics; MacroGenics, Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer Inc; Pieris Pharmaceuticals Inc; Puma Biotechnology; Radius Health; Roche Pharma; sanofi-aventis; Seattle Genetics, Inc.

Dr. Sara Hurvitz, Director of the Breast Cancer Clinical Trials Program at UCLA, reviews key updates in HER2-positive metastatic breast cancer studies presented during the 2020 San Antonio Breast Cancer Symposium (SABCS), which was held virtually in December.

A sub-analysis of patients who had central nervous system disease at baseline demonstrated improved outcomes with neratinib plus capecitabine compared with those receiving lapatinib plus capecitabine in the NALA trial.

Updated results from the DESTINY-breast01 study of trastuzumab deruxtecan show encouraging results in progression-free survival and early overall survival and high rates of durable responses in a heavily pretreated group of patients with metastatic breast cancer, consistent with early results.

In the HER2CLIMB study, patients treated with tucatinib in combination with trastuzumab and capecitabine had clinically meaningful improvement in progression-free survival, overall survival, and objective response rate independent of HR status compared with placebo, and patients with HR+ and HR- breast cancer with brain metastases experienced similar benefits.

--

Sara A. Hurvitz, MD, FACP, Professor of Medicine. Director, Breast Cancer Clinical Trials Program, Division of Hematology-Oncology David Geffen School of Medicine at UCLA
Medical Director, Clinical Research Unit, UCLA Jonsson Comprehensive Cancer Center.

Dr. Hurvitz has received research grants from: Ambrx; Amgen Inc.; Bayer HealthCare Pharmaceuticals; Daiichi Sankyo, Inc.; Dignitana AB; Eli Lilly and Company; Genentech, Inc.; GlaxoSmithKline; Immunomedics; MacroGenics, Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer Inc; Pieris Pharmaceuticals Inc; Puma Biotechnology; Radius Health; Roche Pharma; sanofi-aventis; Seattle Genetics, Inc.

There is a substantial mismatch between patient and physician reports of toxicity during radiotherapy for breast cancer, according to an analysis of nearly 10,000 U.S. patients.

Researchers assessed physician underrecognition of four key symptoms – pain, pruritus, edema, and fatigue – during radiotherapy. Physicians underrecognized one of these four symptoms at least once in 53.2% of patients who reported having at least one substantial symptom.

“Understanding whether physicians detect when their patients are experiencing substantial toxicity is important, not only because recognition of symptoms is necessary for appropriate supportive care, but also because it influences what techniques and treatments we adopt,” said Reshma Jagsi, MD, DPhil, of the University of Michigan, Ann Arbor.

Dr. Jagsi presented the study results at the 2020 San Antonio Breast Cancer Symposium.

The underrecognition of symptoms during radiotherapy may reflect differences in physician or patient behaviors, according to Dr. Jagsi. “It’s absolutely something we need to understand better.”

Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute in Boston, moderated the session where this research was presented and called the work “striking,” noting that it “clearly identifies an important area that needs improvement.”

“We need to do a better job. We as physicians need to listen more to our patients,” said Virginia Kaklamani, MD, of the University of Texas Health Science Center, San Antonio, and codirector of the SABCS 2020 meeting.
 

Comparing patient and physician reports

Dr. Jagsi and colleagues analyzed data on patients who had received radiotherapy after lumpectomy for breast cancer and had completed patient-reported outcome measures (PROs) as part of the Michigan Radiation Oncology Quality Consortium (MROQC). The MROQC registry collects data on patients receiving radiation for breast, lung, and prostate cancers, as well as for bone metastases.

Results of the PROs were compared with physician reports of toxicity as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) system.

The researchers evaluated underrecognition of toxicity in 9,868 patients by comparing 37,593 independent paired observations from patients and their doctors. Patient and physician reports were made on the same day (n = 35,797) or within 3 days of each other (n = 1,796).

The comparison showed underrecognition of all four symptoms assessed – pain, pruritus, edema, and fatigue.

Underrecognition of pain was defined as patients reporting moderate pain while physicians graded pain as absent or as patients reporting severe pain while physicians rated pain as grade 1 or lower. Underrecognition of fatigue, bother from pruritus, or bother from edema were defined as physicians grading these symptoms as absent when patients reported fatigue or bother from pruritus/edema often or all of the time.

The percentage of observations with underrecognized symptoms was 30.9% for moderate to severe pain, 36.7% for frequent bother from pruritus, 51.4% for frequent bother from edema, and 18.8% for severe fatigue.

Factors independently associated with symptom underrecognition were younger age (odds ratio, 1.4 for <50 years and 1.2 for 50-59 years), Black or other non-White race (OR, 1.9 and 1.8, respectively), conventional fractionation (OR, 1.2), not having a supraclavicular field (OR, 1.3), and being treated at an academic center (OR, 1.1).
 

Underreporting worse in the time of COVID?

Data collection for this study ended before the start of the COVID-19 pandemic, but Dr. Jagsi expressed concern that the pandemic could lead to underrecognition of toxicity as well.

“We are doing more virtual visits, and I think the relationships between physicians and patients are a bit more strained,” Dr. Jagsi said. While virtual visits mean that patients can be seen safely, they are “not the same as being in the same room as one another.”

On the other hand, in-person visits during the pandemic may pose challenges as well. The need to wear masks during in-person consultations could lead to a lot of nonverbal communication being missed.

“I wouldn’t be surprised at all if underrecognition were worse in this context,” Dr. Jagsi said.
 

Encourage patients to speak up, use PROs

“I think we need to encourage patients that when we’ve told them that certain side effects are expected, it doesn’t mean that they shouldn’t tell us if they’re bothered by those side effects,” Dr. Jagsi said. “They’re not bothering us. They’re not troubling us to bring those symptoms to our attention, because there actually are things that we can do to help support them through the experience.”

Dr. Jagsi also said PROs should be included in clinical trials. Trials tend to rely on physician assessment of possible toxicity using the CTCAE system, but this can miss important symptoms that patients experience during radiotherapy.

The current study and MROQC were sponsored by Blue Cross Blue Shield of Michigan and the Blue Care Network as part of the BCBSM Value Partnership program. Dr. Jagsi disclosed financial relationships with Amgen, Equity Quotient, Genentech, Vizient, law firms, various foundations, the National Institutes of Health, and BCBSM for the MROQC. Dr. Kaklamani and Dr. Krop disclosed relationships with many pharmaceutical companies.

SOURCE: Jagsi R J et al. SABCS 2020, Abstract GS3-07.

There is a substantial mismatch between patient and physician reports of toxicity during radiotherapy for breast cancer, according to an analysis of nearly 10,000 U.S. patients.

Researchers assessed physician underrecognition of four key symptoms – pain, pruritus, edema, and fatigue – during radiotherapy. Physicians underrecognized one of these four symptoms at least once in 53.2% of patients who reported having at least one substantial symptom.

“Understanding whether physicians detect when their patients are experiencing substantial toxicity is important, not only because recognition of symptoms is necessary for appropriate supportive care, but also because it influences what techniques and treatments we adopt,” said Reshma Jagsi, MD, DPhil, of the University of Michigan, Ann Arbor.

Dr. Jagsi presented the study results at the 2020 San Antonio Breast Cancer Symposium.

The underrecognition of symptoms during radiotherapy may reflect differences in physician or patient behaviors, according to Dr. Jagsi. “It’s absolutely something we need to understand better.”

Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute in Boston, moderated the session where this research was presented and called the work “striking,” noting that it “clearly identifies an important area that needs improvement.”

“We need to do a better job. We as physicians need to listen more to our patients,” said Virginia Kaklamani, MD, of the University of Texas Health Science Center, San Antonio, and codirector of the SABCS 2020 meeting.
 

Comparing patient and physician reports

Dr. Jagsi and colleagues analyzed data on patients who had received radiotherapy after lumpectomy for breast cancer and had completed patient-reported outcome measures (PROs) as part of the Michigan Radiation Oncology Quality Consortium (MROQC). The MROQC registry collects data on patients receiving radiation for breast, lung, and prostate cancers, as well as for bone metastases.

Results of the PROs were compared with physician reports of toxicity as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) system.

The researchers evaluated underrecognition of toxicity in 9,868 patients by comparing 37,593 independent paired observations from patients and their doctors. Patient and physician reports were made on the same day (n = 35,797) or within 3 days of each other (n = 1,796).

The comparison showed underrecognition of all four symptoms assessed – pain, pruritus, edema, and fatigue.

Underrecognition of pain was defined as patients reporting moderate pain while physicians graded pain as absent or as patients reporting severe pain while physicians rated pain as grade 1 or lower. Underrecognition of fatigue, bother from pruritus, or bother from edema were defined as physicians grading these symptoms as absent when patients reported fatigue or bother from pruritus/edema often or all of the time.

The percentage of observations with underrecognized symptoms was 30.9% for moderate to severe pain, 36.7% for frequent bother from pruritus, 51.4% for frequent bother from edema, and 18.8% for severe fatigue.

Factors independently associated with symptom underrecognition were younger age (odds ratio, 1.4 for <50 years and 1.2 for 50-59 years), Black or other non-White race (OR, 1.9 and 1.8, respectively), conventional fractionation (OR, 1.2), not having a supraclavicular field (OR, 1.3), and being treated at an academic center (OR, 1.1).
 

Underreporting worse in the time of COVID?

Data collection for this study ended before the start of the COVID-19 pandemic, but Dr. Jagsi expressed concern that the pandemic could lead to underrecognition of toxicity as well.

“We are doing more virtual visits, and I think the relationships between physicians and patients are a bit more strained,” Dr. Jagsi said. While virtual visits mean that patients can be seen safely, they are “not the same as being in the same room as one another.”

On the other hand, in-person visits during the pandemic may pose challenges as well. The need to wear masks during in-person consultations could lead to a lot of nonverbal communication being missed.

“I wouldn’t be surprised at all if underrecognition were worse in this context,” Dr. Jagsi said.
 

Encourage patients to speak up, use PROs

“I think we need to encourage patients that when we’ve told them that certain side effects are expected, it doesn’t mean that they shouldn’t tell us if they’re bothered by those side effects,” Dr. Jagsi said. “They’re not bothering us. They’re not troubling us to bring those symptoms to our attention, because there actually are things that we can do to help support them through the experience.”

Dr. Jagsi also said PROs should be included in clinical trials. Trials tend to rely on physician assessment of possible toxicity using the CTCAE system, but this can miss important symptoms that patients experience during radiotherapy.

The current study and MROQC were sponsored by Blue Cross Blue Shield of Michigan and the Blue Care Network as part of the BCBSM Value Partnership program. Dr. Jagsi disclosed financial relationships with Amgen, Equity Quotient, Genentech, Vizient, law firms, various foundations, the National Institutes of Health, and BCBSM for the MROQC. Dr. Kaklamani and Dr. Krop disclosed relationships with many pharmaceutical companies.

SOURCE: Jagsi R J et al. SABCS 2020, Abstract GS3-07.

There is a substantial mismatch between patient and physician reports of toxicity during radiotherapy for breast cancer, according to an analysis of nearly 10,000 U.S. patients.

Researchers assessed physician underrecognition of four key symptoms – pain, pruritus, edema, and fatigue – during radiotherapy. Physicians underrecognized one of these four symptoms at least once in 53.2% of patients who reported having at least one substantial symptom.

“Understanding whether physicians detect when their patients are experiencing substantial toxicity is important, not only because recognition of symptoms is necessary for appropriate supportive care, but also because it influences what techniques and treatments we adopt,” said Reshma Jagsi, MD, DPhil, of the University of Michigan, Ann Arbor.

Dr. Jagsi presented the study results at the 2020 San Antonio Breast Cancer Symposium.

The underrecognition of symptoms during radiotherapy may reflect differences in physician or patient behaviors, according to Dr. Jagsi. “It’s absolutely something we need to understand better.”

Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute in Boston, moderated the session where this research was presented and called the work “striking,” noting that it “clearly identifies an important area that needs improvement.”

“We need to do a better job. We as physicians need to listen more to our patients,” said Virginia Kaklamani, MD, of the University of Texas Health Science Center, San Antonio, and codirector of the SABCS 2020 meeting.
 

Comparing patient and physician reports

Dr. Jagsi and colleagues analyzed data on patients who had received radiotherapy after lumpectomy for breast cancer and had completed patient-reported outcome measures (PROs) as part of the Michigan Radiation Oncology Quality Consortium (MROQC). The MROQC registry collects data on patients receiving radiation for breast, lung, and prostate cancers, as well as for bone metastases.

Results of the PROs were compared with physician reports of toxicity as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) system.

The researchers evaluated underrecognition of toxicity in 9,868 patients by comparing 37,593 independent paired observations from patients and their doctors. Patient and physician reports were made on the same day (n = 35,797) or within 3 days of each other (n = 1,796).

The comparison showed underrecognition of all four symptoms assessed – pain, pruritus, edema, and fatigue.

Underrecognition of pain was defined as patients reporting moderate pain while physicians graded pain as absent or as patients reporting severe pain while physicians rated pain as grade 1 or lower. Underrecognition of fatigue, bother from pruritus, or bother from edema were defined as physicians grading these symptoms as absent when patients reported fatigue or bother from pruritus/edema often or all of the time.

The percentage of observations with underrecognized symptoms was 30.9% for moderate to severe pain, 36.7% for frequent bother from pruritus, 51.4% for frequent bother from edema, and 18.8% for severe fatigue.

Factors independently associated with symptom underrecognition were younger age (odds ratio, 1.4 for <50 years and 1.2 for 50-59 years), Black or other non-White race (OR, 1.9 and 1.8, respectively), conventional fractionation (OR, 1.2), not having a supraclavicular field (OR, 1.3), and being treated at an academic center (OR, 1.1).
 

Underreporting worse in the time of COVID?

Data collection for this study ended before the start of the COVID-19 pandemic, but Dr. Jagsi expressed concern that the pandemic could lead to underrecognition of toxicity as well.

“We are doing more virtual visits, and I think the relationships between physicians and patients are a bit more strained,” Dr. Jagsi said. While virtual visits mean that patients can be seen safely, they are “not the same as being in the same room as one another.”

On the other hand, in-person visits during the pandemic may pose challenges as well. The need to wear masks during in-person consultations could lead to a lot of nonverbal communication being missed.

“I wouldn’t be surprised at all if underrecognition were worse in this context,” Dr. Jagsi said.
 

Encourage patients to speak up, use PROs

“I think we need to encourage patients that when we’ve told them that certain side effects are expected, it doesn’t mean that they shouldn’t tell us if they’re bothered by those side effects,” Dr. Jagsi said. “They’re not bothering us. They’re not troubling us to bring those symptoms to our attention, because there actually are things that we can do to help support them through the experience.”

Dr. Jagsi also said PROs should be included in clinical trials. Trials tend to rely on physician assessment of possible toxicity using the CTCAE system, but this can miss important symptoms that patients experience during radiotherapy.

The current study and MROQC were sponsored by Blue Cross Blue Shield of Michigan and the Blue Care Network as part of the BCBSM Value Partnership program. Dr. Jagsi disclosed financial relationships with Amgen, Equity Quotient, Genentech, Vizient, law firms, various foundations, the National Institutes of Health, and BCBSM for the MROQC. Dr. Kaklamani and Dr. Krop disclosed relationships with many pharmaceutical companies.

SOURCE: Jagsi R J et al. SABCS 2020, Abstract GS3-07.

Breast cancer recurrence rates are similar with anastrozole and tamoxifen in postmenopausal women with hormone receptor–positive ductal carcinoma in situ (HR-positive DCIS), according to long-term results of the IBIS-II DCIS trial.

“Our analysis shows that there was really no significant difference in recurrences,” said investigator Ivana Sestak, PhD, of Queen Mary University of London.

Similarly, there were no significant differences in overall deaths or breast cancer deaths. On the other hand, there were “clear differences” in adverse events with the two treatments, Dr. Sestak said.

“[W]e observed an excess of endometrial cancer and ovarian cancers in women who were randomized to tamoxifen and an excess of fractures, strokes, and transient ischemic attacks for women who were randomized to anastrozole,” Dr. Sestak said.

She presented these results at the 2020 San Antonio Breast Cancer Symposium.
 

Comparing IBIS-II DCIS with prior results

“The long-term results of the IBIS-II [DCIS] trial are consistent with previous results,” said Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.

However, the results do contrast with the findings of the NSABP-B35 study, “which demonstrated a very modest advantage to anastrozole that was mostly limited to younger postmenopausal women,” she said.

Indeed, a significant 27% reduction in recurrence was seen with anastrozole, compared with tamoxifen at a median of 9 years of follow-up in the NSABP-B35 study. But, as Dr. Sestak pointed out, that reduction “was mainly observed during the posttreatment follow-up period and not during the active treatment period.”

In the IBIS-II DCIS study, there was a nonsignificant 11% reduction in breast cancer recurrence with anastrozole.

The investigators did examine the potential effect of age on the rate of breast cancer recurrence, but no significant differences were found. They also looked at the active and post–endocrine therapy treatment periods, all showing no benefit of one drug over the other.

“So we clearly cannot replicate the findings of the NSABP-B35 study,” Dr. Sestak acknowledged.
 

IBIS-II DCIS details and results

Aromatase inhibitors such as anastrozole have been shown to be more effective than tamoxifen for preventing recurrence in postmenopausal HR+ women with invasive breast cancer, but it wasn’t previously known if this included women with HR-positive DCIS.

The IBIS-II DCIS study was therefore designed to determine if there was any advantage of anastrazole over tamoxifen. The phase 3 trial enrolled 2,980 postmenopausal women with HR-positive DCIS. They were randomized to 5 years of anastrozole or 5 years of tamoxifen.

“Women were followed up during this active period of treatment by clinic visits,” explained Dr. Sestak. “Thereafter, we collected data via questionnaire, registry data sets, and clinic visits.”

Baseline characteristics were similar between the treatment arms. The median age was about 60 years in both arms. Similar proportions of patients had received hormone replacement therapy (44.2% in the tamoxifen arm and 46.8% in the anastrozole arm) or undergone radiotherapy (71.5% and 70.9%, respectively).

Results showed little difference in breast cancer recurrence rates. At a median follow-up of 11.6 years, the rate of recurrence was 9.7% with tamoxifen and 8.5% with anastrozole (hazard ratio, 0.89; P = .401).

Trends were seen favoring anastrozole in estrogen receptor–positive and HER2-negative women, but this was only while women were being actively treated.

Death rates were similar – 4.2% with anastrozole and 4.5% with tamoxifen (odds ratio, 0.93). There were three breast cancer deaths in each treatment arm.
 

Adverse events could be the deciding factor

“The main take-away from this presentation is that choice of adjuvant endocrine therapy for DCIS should be individualized based primarily on the different side effect profiles of the two medications,” Dr. Moore said.

During the trial, “a significant 34% increase in fractures was observed in women who received anastrozole, compared to tamoxifen [HR, 1.34; P = .013],” Dr. Sestak said.

“We also observed a threefold increase in strokes and transient ischemic attacks with anastrozole, compared to tamoxifen [HR, 3.10; P = .021 for both strokes and transient ischemic attacks],” Dr. Sestak added.

She acknowledged that this finding is inconsistent with what is known about aromatase inhibitors in general. It could be that, rather than anastrozole raising the risk of strokes and transient ischemic attacks, tamoxifen was having a beneficial effect. This could be a result of tamoxifen improving endothelial function by increasing vasodilation, “but it is really not clear what the mechanism is,” Dr. Sestak said.

Also contrary to what is known about tamoxifen was an excess of deaths because of endometrial cancer or ovarian cancers. Wherever possible, the pathology reports had been requested to confirm the cause of death, “so we are pretty sure that they are true ovarian cancers and not some other abdominal tumors,” Dr. Sestak said.

“We did observe very clear differences in terms of adverse events,” she said, adding that “improved understanding of adverse event profiles will help patients with HR-positive DCIS to make an informed decision regarding their treatment.”

The IBIS-II DCIS trial was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, AstraZeneca, and Sanofi Aventis. Two investigators disclosed relationships with AstraZeneca, and one disclosed a relationship with Cancer Research UK. Dr. Sestak and Dr. Moore had no relevant disclosures.

SOURCE: Sestak I et al. SABCS 2020, Abstract GS2-02.

Breast cancer recurrence rates are similar with anastrozole and tamoxifen in postmenopausal women with hormone receptor–positive ductal carcinoma in situ (HR-positive DCIS), according to long-term results of the IBIS-II DCIS trial.

“Our analysis shows that there was really no significant difference in recurrences,” said investigator Ivana Sestak, PhD, of Queen Mary University of London.

Similarly, there were no significant differences in overall deaths or breast cancer deaths. On the other hand, there were “clear differences” in adverse events with the two treatments, Dr. Sestak said.

“[W]e observed an excess of endometrial cancer and ovarian cancers in women who were randomized to tamoxifen and an excess of fractures, strokes, and transient ischemic attacks for women who were randomized to anastrozole,” Dr. Sestak said.

She presented these results at the 2020 San Antonio Breast Cancer Symposium.
 

Comparing IBIS-II DCIS with prior results

“The long-term results of the IBIS-II [DCIS] trial are consistent with previous results,” said Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.

However, the results do contrast with the findings of the NSABP-B35 study, “which demonstrated a very modest advantage to anastrozole that was mostly limited to younger postmenopausal women,” she said.

Indeed, a significant 27% reduction in recurrence was seen with anastrozole, compared with tamoxifen at a median of 9 years of follow-up in the NSABP-B35 study. But, as Dr. Sestak pointed out, that reduction “was mainly observed during the posttreatment follow-up period and not during the active treatment period.”

In the IBIS-II DCIS study, there was a nonsignificant 11% reduction in breast cancer recurrence with anastrozole.

The investigators did examine the potential effect of age on the rate of breast cancer recurrence, but no significant differences were found. They also looked at the active and post–endocrine therapy treatment periods, all showing no benefit of one drug over the other.

“So we clearly cannot replicate the findings of the NSABP-B35 study,” Dr. Sestak acknowledged.
 

IBIS-II DCIS details and results

Aromatase inhibitors such as anastrozole have been shown to be more effective than tamoxifen for preventing recurrence in postmenopausal HR+ women with invasive breast cancer, but it wasn’t previously known if this included women with HR-positive DCIS.

The IBIS-II DCIS study was therefore designed to determine if there was any advantage of anastrazole over tamoxifen. The phase 3 trial enrolled 2,980 postmenopausal women with HR-positive DCIS. They were randomized to 5 years of anastrozole or 5 years of tamoxifen.

“Women were followed up during this active period of treatment by clinic visits,” explained Dr. Sestak. “Thereafter, we collected data via questionnaire, registry data sets, and clinic visits.”

Baseline characteristics were similar between the treatment arms. The median age was about 60 years in both arms. Similar proportions of patients had received hormone replacement therapy (44.2% in the tamoxifen arm and 46.8% in the anastrozole arm) or undergone radiotherapy (71.5% and 70.9%, respectively).

Results showed little difference in breast cancer recurrence rates. At a median follow-up of 11.6 years, the rate of recurrence was 9.7% with tamoxifen and 8.5% with anastrozole (hazard ratio, 0.89; P = .401).

Trends were seen favoring anastrozole in estrogen receptor–positive and HER2-negative women, but this was only while women were being actively treated.

Death rates were similar – 4.2% with anastrozole and 4.5% with tamoxifen (odds ratio, 0.93). There were three breast cancer deaths in each treatment arm.
 

Adverse events could be the deciding factor

“The main take-away from this presentation is that choice of adjuvant endocrine therapy for DCIS should be individualized based primarily on the different side effect profiles of the two medications,” Dr. Moore said.

During the trial, “a significant 34% increase in fractures was observed in women who received anastrozole, compared to tamoxifen [HR, 1.34; P = .013],” Dr. Sestak said.

“We also observed a threefold increase in strokes and transient ischemic attacks with anastrozole, compared to tamoxifen [HR, 3.10; P = .021 for both strokes and transient ischemic attacks],” Dr. Sestak added.

She acknowledged that this finding is inconsistent with what is known about aromatase inhibitors in general. It could be that, rather than anastrozole raising the risk of strokes and transient ischemic attacks, tamoxifen was having a beneficial effect. This could be a result of tamoxifen improving endothelial function by increasing vasodilation, “but it is really not clear what the mechanism is,” Dr. Sestak said.

Also contrary to what is known about tamoxifen was an excess of deaths because of endometrial cancer or ovarian cancers. Wherever possible, the pathology reports had been requested to confirm the cause of death, “so we are pretty sure that they are true ovarian cancers and not some other abdominal tumors,” Dr. Sestak said.

“We did observe very clear differences in terms of adverse events,” she said, adding that “improved understanding of adverse event profiles will help patients with HR-positive DCIS to make an informed decision regarding their treatment.”

The IBIS-II DCIS trial was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, AstraZeneca, and Sanofi Aventis. Two investigators disclosed relationships with AstraZeneca, and one disclosed a relationship with Cancer Research UK. Dr. Sestak and Dr. Moore had no relevant disclosures.

SOURCE: Sestak I et al. SABCS 2020, Abstract GS2-02.

Breast cancer recurrence rates are similar with anastrozole and tamoxifen in postmenopausal women with hormone receptor–positive ductal carcinoma in situ (HR-positive DCIS), according to long-term results of the IBIS-II DCIS trial.

“Our analysis shows that there was really no significant difference in recurrences,” said investigator Ivana Sestak, PhD, of Queen Mary University of London.

Similarly, there were no significant differences in overall deaths or breast cancer deaths. On the other hand, there were “clear differences” in adverse events with the two treatments, Dr. Sestak said.

“[W]e observed an excess of endometrial cancer and ovarian cancers in women who were randomized to tamoxifen and an excess of fractures, strokes, and transient ischemic attacks for women who were randomized to anastrozole,” Dr. Sestak said.

She presented these results at the 2020 San Antonio Breast Cancer Symposium.
 

Comparing IBIS-II DCIS with prior results

“The long-term results of the IBIS-II [DCIS] trial are consistent with previous results,” said Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.

However, the results do contrast with the findings of the NSABP-B35 study, “which demonstrated a very modest advantage to anastrozole that was mostly limited to younger postmenopausal women,” she said.

Indeed, a significant 27% reduction in recurrence was seen with anastrozole, compared with tamoxifen at a median of 9 years of follow-up in the NSABP-B35 study. But, as Dr. Sestak pointed out, that reduction “was mainly observed during the posttreatment follow-up period and not during the active treatment period.”

In the IBIS-II DCIS study, there was a nonsignificant 11% reduction in breast cancer recurrence with anastrozole.

The investigators did examine the potential effect of age on the rate of breast cancer recurrence, but no significant differences were found. They also looked at the active and post–endocrine therapy treatment periods, all showing no benefit of one drug over the other.

“So we clearly cannot replicate the findings of the NSABP-B35 study,” Dr. Sestak acknowledged.
 

IBIS-II DCIS details and results

Aromatase inhibitors such as anastrozole have been shown to be more effective than tamoxifen for preventing recurrence in postmenopausal HR+ women with invasive breast cancer, but it wasn’t previously known if this included women with HR-positive DCIS.

The IBIS-II DCIS study was therefore designed to determine if there was any advantage of anastrazole over tamoxifen. The phase 3 trial enrolled 2,980 postmenopausal women with HR-positive DCIS. They were randomized to 5 years of anastrozole or 5 years of tamoxifen.

“Women were followed up during this active period of treatment by clinic visits,” explained Dr. Sestak. “Thereafter, we collected data via questionnaire, registry data sets, and clinic visits.”

Baseline characteristics were similar between the treatment arms. The median age was about 60 years in both arms. Similar proportions of patients had received hormone replacement therapy (44.2% in the tamoxifen arm and 46.8% in the anastrozole arm) or undergone radiotherapy (71.5% and 70.9%, respectively).

Results showed little difference in breast cancer recurrence rates. At a median follow-up of 11.6 years, the rate of recurrence was 9.7% with tamoxifen and 8.5% with anastrozole (hazard ratio, 0.89; P = .401).

Trends were seen favoring anastrozole in estrogen receptor–positive and HER2-negative women, but this was only while women were being actively treated.

Death rates were similar – 4.2% with anastrozole and 4.5% with tamoxifen (odds ratio, 0.93). There were three breast cancer deaths in each treatment arm.
 

Adverse events could be the deciding factor

“The main take-away from this presentation is that choice of adjuvant endocrine therapy for DCIS should be individualized based primarily on the different side effect profiles of the two medications,” Dr. Moore said.

During the trial, “a significant 34% increase in fractures was observed in women who received anastrozole, compared to tamoxifen [HR, 1.34; P = .013],” Dr. Sestak said.

“We also observed a threefold increase in strokes and transient ischemic attacks with anastrozole, compared to tamoxifen [HR, 3.10; P = .021 for both strokes and transient ischemic attacks],” Dr. Sestak added.

She acknowledged that this finding is inconsistent with what is known about aromatase inhibitors in general. It could be that, rather than anastrozole raising the risk of strokes and transient ischemic attacks, tamoxifen was having a beneficial effect. This could be a result of tamoxifen improving endothelial function by increasing vasodilation, “but it is really not clear what the mechanism is,” Dr. Sestak said.

Also contrary to what is known about tamoxifen was an excess of deaths because of endometrial cancer or ovarian cancers. Wherever possible, the pathology reports had been requested to confirm the cause of death, “so we are pretty sure that they are true ovarian cancers and not some other abdominal tumors,” Dr. Sestak said.

“We did observe very clear differences in terms of adverse events,” she said, adding that “improved understanding of adverse event profiles will help patients with HR-positive DCIS to make an informed decision regarding their treatment.”

The IBIS-II DCIS trial was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, AstraZeneca, and Sanofi Aventis. Two investigators disclosed relationships with AstraZeneca, and one disclosed a relationship with Cancer Research UK. Dr. Sestak and Dr. Moore had no relevant disclosures.

SOURCE: Sestak I et al. SABCS 2020, Abstract GS2-02.

What is more stressful in the mind of a patient – a diagnosis of cancer or infertility? An infertile woman’s anxiety and depression scores are equivalent to one with cancer (J Psychosom Obstet Gynecol. 1993;14 Suppl:45-52). These two diseases intersect in the burgeoning field of oncofertility, the collaboration of oncology with reproductive endocrinology to offer patients the option of fertility preservation. The term oncofertility was first coined by Teresa Woodruff, PhD, in 2005 during her invited lecture at the University of Calgary symposium called “Pushing the Boundaries – Advances that Will Change the World in 20 Years.” Her prediction has reached its fruition. This article will review fertility preservation options for female oncology patients.

The ability for oncofertility to exist is the result of improved cancer survival rates and advances in reproductive medicine. Improvements in the treatment of cancer enable many young women to survive and focus on the potential of having a family. Malignancies striking young people, particularly breast, lymphoma, and melanoma, have encouraging 5-year survival rates. If invasive cancer is located only in the breast (affecting 62% of women diagnosed), the 5-year survival rate is 99%. For all with Hodgkin lymphoma, the 5-year survival is 87%, increasing to 92% if the cancer is found in its earliest stages. Among all people with melanoma of the skin, from the time of initial diagnosis, the 5-year survival is 92%.

Long-term survival is expected for 80% of children and adolescents diagnosed with cancer (Obstet Gynecol. 2010;116: 1171-83).
 

Iatrogenic effects

The reproductive risk of cancer treatment is gonadotoxicity and the subsequent iatrogenic primary ovarian insufficiency (POI, prior termed premature ovarian failure) or infertility.

Chemotherapy with alkylating agents, such as cyclophosphamide, is associated with the greatest chance of amenorrhea (Breast Cancer Res Treat. 2014;145:113-28). Chemotherapy with cyclophosphamide, methotrexate, and 5 fluorouracil (CMF – commonly used for the treatment of breast cancer) will usually result in loss of ovarian function in 33% of women under age 30, 50% of women aged 30-35, 75% of women aged 35-40, and 95% of women over age 40 (J Clin Oncol. 2006;24:5769-79).

The dose at which 50% of oocytes are lost due to radiation is under 2 Gy (Hum Reprod. 2003;18:117-21). Unfortunately, the minimum dose decreases with advancing age of the woman, contributed by natural diminishing reserve and an increase in radiosensitivity of oocytes. Age, proximity of the radiation field to the ovaries, and total dose are important factors determining risk of POI. For brain tumors, cranial irradiation may result in hypothalamic amenorrhea.
 

Protection

The use of GnRH agonist for 6 months during chemotherapy has been controversial with mixed results in avoiding ovarian failure. A recent study suggests a GnRH agonist does reduce the prevalence of POI (J Clin Oncol. 2018;36:1981-90) in women treated for breast cancer but the subsequent ovarian reserve is low (Ann Oncol. 2017;28:1811-6). There are not enough data now to consider this the sole viable option for all patients to preserve fertility.

Patients requiring local pelvic radiation treatment may benefit from transposition of the ovaries to sites away from maximal radiation exposure.
 

Oocyte cryopreservation (OC) and ovarian tissue cryopreservation (OTC)

Since 2012, the American Society for Reproductive Medicine lifted the experimental designation on OC and, last year, the society removed the same label for OTC, providing an additional fertility preservation option.

Ovarian stimulation and egg retrieval for OC can now occur literally within 2 weeks because of a random start protocol whereby women are stimulated any day in their cycle, pre- and post ovulation. Studies have shown equivalent yield of oocytes.

OC followed by thawing for subsequent fertilization and embryo transfer is employed as a routine matter with egg donation cycles. While there remains debate over whether live birth rates using frozen eggs are inferior to fresh eggs, a learning curve with the new technology may be the important factor (Obstet Gynecol. 2020;135:709-16).

When urgent cancer treatment precludes ovarian stimulation for OC, then OTC is a viable option. Another population that could benefit from OTC are prepubertal girls facing gonadotoxic therapy. More research is required to determine the quality of eggs obtained through ovarian stimulation in adolescent and young adult patients. While leukemic patients are eligible for OTC, there is concern about reseeding malignant cells with future autologous transplantation of tissue.

OTC involves obtaining ovarian cortical tissue, dissecting the tissue into small fragments, and cryopreserving it using either a slow-cool technique or vitrification. Orthotopic transplantation has been the most successful method for using ovarian tissue in humans. To date, live birth rates are modest (Fertil Steril. 2015;104:1097-8).

Recent research has combined the freezing of both mature and immature eggs, the latter undergoing IVM (in-vitro maturation) to maximize the potential for fertilizable eggs. Women with polycystic ovary syndrome and certain cancers or medical conditions that warrant avoiding supraphysiologic levels of estradiol from ovarian stimulation, may benefit from the retrieval of immature eggs from unstimulated ovaries.

Pregnancy outcomes using embryos created from ovaries recently exposed to chemotherapy in humans are not known but animal studies suggest there may be higher rates of miscarriage and birth defects.
 

Breast cancer – a special scenario

With every breast cancer patient, I review the theoretical concern over increasing estradiol levels during an IVF stimulation cycle with the potential impact on her cancer prognosis. Fortunately, the literature has not demonstrated an increased risk of breast cancer or recurrence after undergoing an IVF cycle. Currently, the use of aromatase inhibitors with gonadotropins along with a GnRH-antagonist is the protocol to maintain a lower estradiol level during stimulation, which may be of benefit for breast cancer prognosis. The use of aromatase inhibitors is an off-label indication for fertility with no definitive evidence of teratogenicity. Preimplantation genetic testing of embryos is available and approved by the American Society for Reproductive Medicine for BRCA gene mutation patients.

Oncofertility is an exciting field to allow cancer survivors the option for a biological child. We recommend all our cancer patients meet with our reproductive psychologist to assist in coping with the overwhelming information presented in a short time frame.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

What is more stressful in the mind of a patient – a diagnosis of cancer or infertility? An infertile woman’s anxiety and depression scores are equivalent to one with cancer (J Psychosom Obstet Gynecol. 1993;14 Suppl:45-52). These two diseases intersect in the burgeoning field of oncofertility, the collaboration of oncology with reproductive endocrinology to offer patients the option of fertility preservation. The term oncofertility was first coined by Teresa Woodruff, PhD, in 2005 during her invited lecture at the University of Calgary symposium called “Pushing the Boundaries – Advances that Will Change the World in 20 Years.” Her prediction has reached its fruition. This article will review fertility preservation options for female oncology patients.

The ability for oncofertility to exist is the result of improved cancer survival rates and advances in reproductive medicine. Improvements in the treatment of cancer enable many young women to survive and focus on the potential of having a family. Malignancies striking young people, particularly breast, lymphoma, and melanoma, have encouraging 5-year survival rates. If invasive cancer is located only in the breast (affecting 62% of women diagnosed), the 5-year survival rate is 99%. For all with Hodgkin lymphoma, the 5-year survival is 87%, increasing to 92% if the cancer is found in its earliest stages. Among all people with melanoma of the skin, from the time of initial diagnosis, the 5-year survival is 92%.

Long-term survival is expected for 80% of children and adolescents diagnosed with cancer (Obstet Gynecol. 2010;116: 1171-83).
 

Iatrogenic effects

The reproductive risk of cancer treatment is gonadotoxicity and the subsequent iatrogenic primary ovarian insufficiency (POI, prior termed premature ovarian failure) or infertility.

Chemotherapy with alkylating agents, such as cyclophosphamide, is associated with the greatest chance of amenorrhea (Breast Cancer Res Treat. 2014;145:113-28). Chemotherapy with cyclophosphamide, methotrexate, and 5 fluorouracil (CMF – commonly used for the treatment of breast cancer) will usually result in loss of ovarian function in 33% of women under age 30, 50% of women aged 30-35, 75% of women aged 35-40, and 95% of women over age 40 (J Clin Oncol. 2006;24:5769-79).

The dose at which 50% of oocytes are lost due to radiation is under 2 Gy (Hum Reprod. 2003;18:117-21). Unfortunately, the minimum dose decreases with advancing age of the woman, contributed by natural diminishing reserve and an increase in radiosensitivity of oocytes. Age, proximity of the radiation field to the ovaries, and total dose are important factors determining risk of POI. For brain tumors, cranial irradiation may result in hypothalamic amenorrhea.
 

Protection

The use of GnRH agonist for 6 months during chemotherapy has been controversial with mixed results in avoiding ovarian failure. A recent study suggests a GnRH agonist does reduce the prevalence of POI (J Clin Oncol. 2018;36:1981-90) in women treated for breast cancer but the subsequent ovarian reserve is low (Ann Oncol. 2017;28:1811-6). There are not enough data now to consider this the sole viable option for all patients to preserve fertility.

Patients requiring local pelvic radiation treatment may benefit from transposition of the ovaries to sites away from maximal radiation exposure.
 

Oocyte cryopreservation (OC) and ovarian tissue cryopreservation (OTC)

Since 2012, the American Society for Reproductive Medicine lifted the experimental designation on OC and, last year, the society removed the same label for OTC, providing an additional fertility preservation option.

Ovarian stimulation and egg retrieval for OC can now occur literally within 2 weeks because of a random start protocol whereby women are stimulated any day in their cycle, pre- and post ovulation. Studies have shown equivalent yield of oocytes.

OC followed by thawing for subsequent fertilization and embryo transfer is employed as a routine matter with egg donation cycles. While there remains debate over whether live birth rates using frozen eggs are inferior to fresh eggs, a learning curve with the new technology may be the important factor (Obstet Gynecol. 2020;135:709-16).

When urgent cancer treatment precludes ovarian stimulation for OC, then OTC is a viable option. Another population that could benefit from OTC are prepubertal girls facing gonadotoxic therapy. More research is required to determine the quality of eggs obtained through ovarian stimulation in adolescent and young adult patients. While leukemic patients are eligible for OTC, there is concern about reseeding malignant cells with future autologous transplantation of tissue.

OTC involves obtaining ovarian cortical tissue, dissecting the tissue into small fragments, and cryopreserving it using either a slow-cool technique or vitrification. Orthotopic transplantation has been the most successful method for using ovarian tissue in humans. To date, live birth rates are modest (Fertil Steril. 2015;104:1097-8).

Recent research has combined the freezing of both mature and immature eggs, the latter undergoing IVM (in-vitro maturation) to maximize the potential for fertilizable eggs. Women with polycystic ovary syndrome and certain cancers or medical conditions that warrant avoiding supraphysiologic levels of estradiol from ovarian stimulation, may benefit from the retrieval of immature eggs from unstimulated ovaries.

Pregnancy outcomes using embryos created from ovaries recently exposed to chemotherapy in humans are not known but animal studies suggest there may be higher rates of miscarriage and birth defects.
 

Breast cancer – a special scenario

With every breast cancer patient, I review the theoretical concern over increasing estradiol levels during an IVF stimulation cycle with the potential impact on her cancer prognosis. Fortunately, the literature has not demonstrated an increased risk of breast cancer or recurrence after undergoing an IVF cycle. Currently, the use of aromatase inhibitors with gonadotropins along with a GnRH-antagonist is the protocol to maintain a lower estradiol level during stimulation, which may be of benefit for breast cancer prognosis. The use of aromatase inhibitors is an off-label indication for fertility with no definitive evidence of teratogenicity. Preimplantation genetic testing of embryos is available and approved by the American Society for Reproductive Medicine for BRCA gene mutation patients.

Oncofertility is an exciting field to allow cancer survivors the option for a biological child. We recommend all our cancer patients meet with our reproductive psychologist to assist in coping with the overwhelming information presented in a short time frame.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

What is more stressful in the mind of a patient – a diagnosis of cancer or infertility? An infertile woman’s anxiety and depression scores are equivalent to one with cancer (J Psychosom Obstet Gynecol. 1993;14 Suppl:45-52). These two diseases intersect in the burgeoning field of oncofertility, the collaboration of oncology with reproductive endocrinology to offer patients the option of fertility preservation. The term oncofertility was first coined by Teresa Woodruff, PhD, in 2005 during her invited lecture at the University of Calgary symposium called “Pushing the Boundaries – Advances that Will Change the World in 20 Years.” Her prediction has reached its fruition. This article will review fertility preservation options for female oncology patients.

The ability for oncofertility to exist is the result of improved cancer survival rates and advances in reproductive medicine. Improvements in the treatment of cancer enable many young women to survive and focus on the potential of having a family. Malignancies striking young people, particularly breast, lymphoma, and melanoma, have encouraging 5-year survival rates. If invasive cancer is located only in the breast (affecting 62% of women diagnosed), the 5-year survival rate is 99%. For all with Hodgkin lymphoma, the 5-year survival is 87%, increasing to 92% if the cancer is found in its earliest stages. Among all people with melanoma of the skin, from the time of initial diagnosis, the 5-year survival is 92%.

Long-term survival is expected for 80% of children and adolescents diagnosed with cancer (Obstet Gynecol. 2010;116: 1171-83).
 

Iatrogenic effects

The reproductive risk of cancer treatment is gonadotoxicity and the subsequent iatrogenic primary ovarian insufficiency (POI, prior termed premature ovarian failure) or infertility.

Chemotherapy with alkylating agents, such as cyclophosphamide, is associated with the greatest chance of amenorrhea (Breast Cancer Res Treat. 2014;145:113-28). Chemotherapy with cyclophosphamide, methotrexate, and 5 fluorouracil (CMF – commonly used for the treatment of breast cancer) will usually result in loss of ovarian function in 33% of women under age 30, 50% of women aged 30-35, 75% of women aged 35-40, and 95% of women over age 40 (J Clin Oncol. 2006;24:5769-79).

The dose at which 50% of oocytes are lost due to radiation is under 2 Gy (Hum Reprod. 2003;18:117-21). Unfortunately, the minimum dose decreases with advancing age of the woman, contributed by natural diminishing reserve and an increase in radiosensitivity of oocytes. Age, proximity of the radiation field to the ovaries, and total dose are important factors determining risk of POI. For brain tumors, cranial irradiation may result in hypothalamic amenorrhea.
 

Protection

The use of GnRH agonist for 6 months during chemotherapy has been controversial with mixed results in avoiding ovarian failure. A recent study suggests a GnRH agonist does reduce the prevalence of POI (J Clin Oncol. 2018;36:1981-90) in women treated for breast cancer but the subsequent ovarian reserve is low (Ann Oncol. 2017;28:1811-6). There are not enough data now to consider this the sole viable option for all patients to preserve fertility.

Patients requiring local pelvic radiation treatment may benefit from transposition of the ovaries to sites away from maximal radiation exposure.
 

Oocyte cryopreservation (OC) and ovarian tissue cryopreservation (OTC)

Since 2012, the American Society for Reproductive Medicine lifted the experimental designation on OC and, last year, the society removed the same label for OTC, providing an additional fertility preservation option.

Ovarian stimulation and egg retrieval for OC can now occur literally within 2 weeks because of a random start protocol whereby women are stimulated any day in their cycle, pre- and post ovulation. Studies have shown equivalent yield of oocytes.

OC followed by thawing for subsequent fertilization and embryo transfer is employed as a routine matter with egg donation cycles. While there remains debate over whether live birth rates using frozen eggs are inferior to fresh eggs, a learning curve with the new technology may be the important factor (Obstet Gynecol. 2020;135:709-16).

When urgent cancer treatment precludes ovarian stimulation for OC, then OTC is a viable option. Another population that could benefit from OTC are prepubertal girls facing gonadotoxic therapy. More research is required to determine the quality of eggs obtained through ovarian stimulation in adolescent and young adult patients. While leukemic patients are eligible for OTC, there is concern about reseeding malignant cells with future autologous transplantation of tissue.

OTC involves obtaining ovarian cortical tissue, dissecting the tissue into small fragments, and cryopreserving it using either a slow-cool technique or vitrification. Orthotopic transplantation has been the most successful method for using ovarian tissue in humans. To date, live birth rates are modest (Fertil Steril. 2015;104:1097-8).

Recent research has combined the freezing of both mature and immature eggs, the latter undergoing IVM (in-vitro maturation) to maximize the potential for fertilizable eggs. Women with polycystic ovary syndrome and certain cancers or medical conditions that warrant avoiding supraphysiologic levels of estradiol from ovarian stimulation, may benefit from the retrieval of immature eggs from unstimulated ovaries.

Pregnancy outcomes using embryos created from ovaries recently exposed to chemotherapy in humans are not known but animal studies suggest there may be higher rates of miscarriage and birth defects.
 

Breast cancer – a special scenario

With every breast cancer patient, I review the theoretical concern over increasing estradiol levels during an IVF stimulation cycle with the potential impact on her cancer prognosis. Fortunately, the literature has not demonstrated an increased risk of breast cancer or recurrence after undergoing an IVF cycle. Currently, the use of aromatase inhibitors with gonadotropins along with a GnRH-antagonist is the protocol to maintain a lower estradiol level during stimulation, which may be of benefit for breast cancer prognosis. The use of aromatase inhibitors is an off-label indication for fertility with no definitive evidence of teratogenicity. Preimplantation genetic testing of embryos is available and approved by the American Society for Reproductive Medicine for BRCA gene mutation patients.

Oncofertility is an exciting field to allow cancer survivors the option for a biological child. We recommend all our cancer patients meet with our reproductive psychologist to assist in coping with the overwhelming information presented in a short time frame.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and associate professor of obstetrics and gynecology at the University of Central Florida, Orlando.

Long-term cosmetic and toxicity outcomes are good for both accelerated partial breast irradiation (APBI) delivered with 3D-conformal radiotherapy and whole-breast irradiation (WBI), with the latter having a slight edge, the IRMA trial shows.

Findings were reported at the European Society for Radiology and Oncology 2020 Online Congress by Bruno Meduri, MD, a radiation oncologist at University Hospital of Modena, Italy.

Uptake of APBI has increased since it was approved nearly 2 decades ago. However, its long-term outcomes are still being parsed, and issues such as appropriate patient selection and optimal delivery technique are still being clarified (Curr Breast Cancer Rep. 2020;18:1-10).

IRMA is a European, multicenter, phase 3 randomized controlled trial conducted among 3,279 women aged 49 years and older who underwent breast-conserving surgery for early-stage breast cancer (measuring <3 cm in diameter, and pathologic N0 or N1) with negative resection margins.

The women were randomized to APBI using 3D-conformal radiotherapy (38.5 Gy in 10 fractions, twice daily) or conventional or hypofractionated WBI (50.0 Gy in 25 fractions, once daily). All additionally received adjuvant therapy according to institutional guidelines.

Patients and physicians separately rated cosmetic outcomes on a 4-point scale using the untreated breast as a reference, and toxicity was graded with the Radiation Therapy Oncology Group (RTOG) scale.

Over a median follow-up of 5 years, patients rated cosmesis more favorably than physicians did at all time points, and there was a trend toward slight worsening of cosmesis in the APBI group with time, Dr. Meduri reported.

At 1 year, cosmesis did not differ significantly between treatment groups regardless of the rater. But compared with the WBI group, the APBI group more often had patient-rated fair to poor cosmesis at 3 years (12.7% vs. 9.4%; P =.02) and at 5 years (15.0% vs. 10.1%; P = .007), as well as physician-rated fair to poor cosmesis at 3 years (18.0% vs. 13.1%; P = .003) and at 5 years (18.4% vs. 14.2%; P = .04).

Women treated with APBI had less acute skin toxicity (P < .001), with 4.9% developing grade 2 toxicity, compared with 21.4% of peers treated with WBI. Late skin toxicity was also less common in the APBI group overall (P < .001), but the rate of grade 3 or 4 late skin toxicity was similar.

On the other hand, the APBI group had more late bone toxicity overall (P < .001) and late bone toxicity of grade 3 or 4 (1.0% vs. 0%; P < .05), as well as more late soft tissue (subcutaneous) toxicity overall (P < .001) and late soft tissue toxicity of grade 3 or 4 (2.6% vs. 1.1%; P < .05).

The two groups had essentially the same late lung toxicity.

Women treated with APBI had higher 5-year cumulative incidences of soft tissue toxicity of grade 2 or worse (29.7% vs. 17.9%; P < .0001) and grade 3 or worse (2.6% vs. 1.1%; P = .0016). Cumulative incidences of skin toxicity of these grades did not differ significantly.

Importantly, the prevalences of late soft tissue and skin toxicity at 5 years were much lower than the cumulative incidences, Dr. Meduri noted. “This means that the side effects in some patients tend to resolve over time.”

Although the prevalence of grade 2-4 skin toxicity increased slightly at 3 years and 5 years in both groups, the prevalence of grade 2-4 soft tissue toxicity was stable.

Finally, the volume that received at least 38.5 Gy of radiation was higher for patients who developed late grade 3 or 4 bone toxicity than for those who did not (2.1 vs. 0.82 cc; P = .027), whereas other dosimetric parameters were similar.

“The toxicity of the whole cohort was very low,” Dr. Meduri summarized. “APBI was associated with a slightly higher rate of late soft tissue and bone toxicity, with a slight decrease in cosmetic outcome at 5 years. But longer follow-up is needed to confirm these results.”

The IRMA findings confirm previous results from the RAPID trial showing that APBI delivered via 3D-conformal radiotherapy may be associated with increased rates of toxicity, Chirag Shah, MD, a radiation oncologist at the Cleveland Clinic in Ohio, said in an interview.

SOURCE: Meduri B et al. ESTRO 2020. Abstract OC-0611.

Long-term cosmetic and toxicity outcomes are good for both accelerated partial breast irradiation (APBI) delivered with 3D-conformal radiotherapy and whole-breast irradiation (WBI), with the latter having a slight edge, the IRMA trial shows.

Findings were reported at the European Society for Radiology and Oncology 2020 Online Congress by Bruno Meduri, MD, a radiation oncologist at University Hospital of Modena, Italy.

Uptake of APBI has increased since it was approved nearly 2 decades ago. However, its long-term outcomes are still being parsed, and issues such as appropriate patient selection and optimal delivery technique are still being clarified (Curr Breast Cancer Rep. 2020;18:1-10).

IRMA is a European, multicenter, phase 3 randomized controlled trial conducted among 3,279 women aged 49 years and older who underwent breast-conserving surgery for early-stage breast cancer (measuring <3 cm in diameter, and pathologic N0 or N1) with negative resection margins.

The women were randomized to APBI using 3D-conformal radiotherapy (38.5 Gy in 10 fractions, twice daily) or conventional or hypofractionated WBI (50.0 Gy in 25 fractions, once daily). All additionally received adjuvant therapy according to institutional guidelines.

Patients and physicians separately rated cosmetic outcomes on a 4-point scale using the untreated breast as a reference, and toxicity was graded with the Radiation Therapy Oncology Group (RTOG) scale.

Over a median follow-up of 5 years, patients rated cosmesis more favorably than physicians did at all time points, and there was a trend toward slight worsening of cosmesis in the APBI group with time, Dr. Meduri reported.

At 1 year, cosmesis did not differ significantly between treatment groups regardless of the rater. But compared with the WBI group, the APBI group more often had patient-rated fair to poor cosmesis at 3 years (12.7% vs. 9.4%; P =.02) and at 5 years (15.0% vs. 10.1%; P = .007), as well as physician-rated fair to poor cosmesis at 3 years (18.0% vs. 13.1%; P = .003) and at 5 years (18.4% vs. 14.2%; P = .04).

Women treated with APBI had less acute skin toxicity (P < .001), with 4.9% developing grade 2 toxicity, compared with 21.4% of peers treated with WBI. Late skin toxicity was also less common in the APBI group overall (P < .001), but the rate of grade 3 or 4 late skin toxicity was similar.

On the other hand, the APBI group had more late bone toxicity overall (P < .001) and late bone toxicity of grade 3 or 4 (1.0% vs. 0%; P < .05), as well as more late soft tissue (subcutaneous) toxicity overall (P < .001) and late soft tissue toxicity of grade 3 or 4 (2.6% vs. 1.1%; P < .05).

The two groups had essentially the same late lung toxicity.

Women treated with APBI had higher 5-year cumulative incidences of soft tissue toxicity of grade 2 or worse (29.7% vs. 17.9%; P < .0001) and grade 3 or worse (2.6% vs. 1.1%; P = .0016). Cumulative incidences of skin toxicity of these grades did not differ significantly.

Importantly, the prevalences of late soft tissue and skin toxicity at 5 years were much lower than the cumulative incidences, Dr. Meduri noted. “This means that the side effects in some patients tend to resolve over time.”

Although the prevalence of grade 2-4 skin toxicity increased slightly at 3 years and 5 years in both groups, the prevalence of grade 2-4 soft tissue toxicity was stable.

Finally, the volume that received at least 38.5 Gy of radiation was higher for patients who developed late grade 3 or 4 bone toxicity than for those who did not (2.1 vs. 0.82 cc; P = .027), whereas other dosimetric parameters were similar.

“The toxicity of the whole cohort was very low,” Dr. Meduri summarized. “APBI was associated with a slightly higher rate of late soft tissue and bone toxicity, with a slight decrease in cosmetic outcome at 5 years. But longer follow-up is needed to confirm these results.”

The IRMA findings confirm previous results from the RAPID trial showing that APBI delivered via 3D-conformal radiotherapy may be associated with increased rates of toxicity, Chirag Shah, MD, a radiation oncologist at the Cleveland Clinic in Ohio, said in an interview.

SOURCE: Meduri B et al. ESTRO 2020. Abstract OC-0611.

Long-term cosmetic and toxicity outcomes are good for both accelerated partial breast irradiation (APBI) delivered with 3D-conformal radiotherapy and whole-breast irradiation (WBI), with the latter having a slight edge, the IRMA trial shows.

Findings were reported at the European Society for Radiology and Oncology 2020 Online Congress by Bruno Meduri, MD, a radiation oncologist at University Hospital of Modena, Italy.

Uptake of APBI has increased since it was approved nearly 2 decades ago. However, its long-term outcomes are still being parsed, and issues such as appropriate patient selection and optimal delivery technique are still being clarified (Curr Breast Cancer Rep. 2020;18:1-10).

IRMA is a European, multicenter, phase 3 randomized controlled trial conducted among 3,279 women aged 49 years and older who underwent breast-conserving surgery for early-stage breast cancer (measuring <3 cm in diameter, and pathologic N0 or N1) with negative resection margins.

The women were randomized to APBI using 3D-conformal radiotherapy (38.5 Gy in 10 fractions, twice daily) or conventional or hypofractionated WBI (50.0 Gy in 25 fractions, once daily). All additionally received adjuvant therapy according to institutional guidelines.

Patients and physicians separately rated cosmetic outcomes on a 4-point scale using the untreated breast as a reference, and toxicity was graded with the Radiation Therapy Oncology Group (RTOG) scale.

Over a median follow-up of 5 years, patients rated cosmesis more favorably than physicians did at all time points, and there was a trend toward slight worsening of cosmesis in the APBI group with time, Dr. Meduri reported.

At 1 year, cosmesis did not differ significantly between treatment groups regardless of the rater. But compared with the WBI group, the APBI group more often had patient-rated fair to poor cosmesis at 3 years (12.7% vs. 9.4%; P =.02) and at 5 years (15.0% vs. 10.1%; P = .007), as well as physician-rated fair to poor cosmesis at 3 years (18.0% vs. 13.1%; P = .003) and at 5 years (18.4% vs. 14.2%; P = .04).

Women treated with APBI had less acute skin toxicity (P < .001), with 4.9% developing grade 2 toxicity, compared with 21.4% of peers treated with WBI. Late skin toxicity was also less common in the APBI group overall (P < .001), but the rate of grade 3 or 4 late skin toxicity was similar.

On the other hand, the APBI group had more late bone toxicity overall (P < .001) and late bone toxicity of grade 3 or 4 (1.0% vs. 0%; P < .05), as well as more late soft tissue (subcutaneous) toxicity overall (P < .001) and late soft tissue toxicity of grade 3 or 4 (2.6% vs. 1.1%; P < .05).

The two groups had essentially the same late lung toxicity.

Women treated with APBI had higher 5-year cumulative incidences of soft tissue toxicity of grade 2 or worse (29.7% vs. 17.9%; P < .0001) and grade 3 or worse (2.6% vs. 1.1%; P = .0016). Cumulative incidences of skin toxicity of these grades did not differ significantly.

Importantly, the prevalences of late soft tissue and skin toxicity at 5 years were much lower than the cumulative incidences, Dr. Meduri noted. “This means that the side effects in some patients tend to resolve over time.”

Although the prevalence of grade 2-4 skin toxicity increased slightly at 3 years and 5 years in both groups, the prevalence of grade 2-4 soft tissue toxicity was stable.

Finally, the volume that received at least 38.5 Gy of radiation was higher for patients who developed late grade 3 or 4 bone toxicity than for those who did not (2.1 vs. 0.82 cc; P = .027), whereas other dosimetric parameters were similar.

“The toxicity of the whole cohort was very low,” Dr. Meduri summarized. “APBI was associated with a slightly higher rate of late soft tissue and bone toxicity, with a slight decrease in cosmetic outcome at 5 years. But longer follow-up is needed to confirm these results.”

The IRMA findings confirm previous results from the RAPID trial showing that APBI delivered via 3D-conformal radiotherapy may be associated with increased rates of toxicity, Chirag Shah, MD, a radiation oncologist at the Cleveland Clinic in Ohio, said in an interview.

SOURCE: Meduri B et al. ESTRO 2020. Abstract OC-0611.

Skipping whole-breast adjuvant radiotherapy does not appear to affect long-term survival in women age 65 and older who have had surgery for early-stage, hormone receptor–positive (HR+) breast cancer, according to 10-year follow-up of the phase 3 PRIME-2 study.

Although the risk for local recurrence was higher among patients who did not receive radiotherapy, the absolute risk for recurrence was still low, said study investigator Ian Kunkler, MRCPUK, FRCR, of Western General Hospital, University of Edinburgh in Scotland.

Dr. Kunkler presented results from PRIME-2 at the 2020 San Antonio Breast Cancer Symposium.

“In older patients, we have to carefully balance benefits [of radiotherapy] in terms of local control and survival against toxicities,” Dr. Kunkler said in an interview.

Omitting radiotherapy could help women avoid complications such as fatigue, changes to lung function, and an increased risk of cardiovascular damage.

“We think that these results should provide some reassurance that the omission of radiotherapy could be an option,” Dr. Kunkler said.
 

PRIME-2 results

The PRIME-2 study was a randomized trial that recruited 1,326 women with histologically confirmed, unilateral invasive breast cancer who were all 65 years or older.

For inclusion, the women had to have a tumor measuring 3 cm or less, have no nodal involvement, and be about to undergo breast-conserving surgery. Women also needed to be HR+ and be treated with adjuvant endocrine therapy.

The women were randomized 1:1 to receive adjuvant whole-breast irradiation at a dosing schedule of 40-50 Gy in 15-25 fractions or no radiotherapy in addition to adjuvant endocrine therapy.

The primary endpoint was the recurrence of breast cancer in the same breast at 10 years. There was a significantly lower rate of ipsilateral recurrence with radiotherapy than without it, at 0.9% and 9.8%, respectively (P = .00008).

Similarly, the 10-year rate of regional recurrence was significantly lower in the radiotherapy arm than in the no-radiotherapy arm (0.5% vs. 2.3%, P = .014).

However, there was no significant difference in the radiotherapy and nonradiotherapy arms when it came to distant recurrence (3.6% vs. 1.9%, P = .07), contralateral recurrence (2.2% vs. 1.2%, P = .20), or new, non–breast cancer (8.7% vs. 10.2%, P = .41).

The overall survival estimate at 10 years was 80.4% in women who did not receive radiotherapy and 81.0% in those who did (P = .68). Rates of metastasis-free survival were also similar (98.1% vs. 96.4%, P = .28).

“Most of these women are dying from non–breast cancer causes, reflecting the impact of competitive causes of non–breast cancer mortality,” Dr. Kunkler said.
 

Implications for practice

The current findings build on prior findings from the PRIME-2 study 5 years ago, which showed a small benefit of postoperative radiotherapy over no radiotherapy in reducing the rate of local recurrence. This led to the recommendation that postoperative radiotherapy might be safely omitted in some older women and influenced U.K. practice.

Indeed, Dr. Kunkler observed that U.K. guidelines have pretty much adopted the entry criteria for the PRIME-2 study (HR+, axillary node-negative [N0], T1–T2 up to 3 cm at the longest dimension, and clear margins) for the omission of radiotherapy.

“It’s had much less impact in the United States, where the usage of radiotherapy after breast-conserving surgery still remains very high,” Dr. Kunkler said.

He acknowledged that the current U.S. guidelines include the omission of radiotherapy in older women, but only those with much smaller (T1, N0) tumors, based on the findings of the Cancer and Leukemia Group B (CALGB) 9343 study.

“The findings from PRIME-2 so far seem consistent with long-term findings from CALGB 9343,” Matthew Katz, MD, of Lowell (Mass.) General Hospital Cancer Center, said in an interview.

SOURCE: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.

Skipping whole-breast adjuvant radiotherapy does not appear to affect long-term survival in women age 65 and older who have had surgery for early-stage, hormone receptor–positive (HR+) breast cancer, according to 10-year follow-up of the phase 3 PRIME-2 study.

Although the risk for local recurrence was higher among patients who did not receive radiotherapy, the absolute risk for recurrence was still low, said study investigator Ian Kunkler, MRCPUK, FRCR, of Western General Hospital, University of Edinburgh in Scotland.

Dr. Kunkler presented results from PRIME-2 at the 2020 San Antonio Breast Cancer Symposium.

“In older patients, we have to carefully balance benefits [of radiotherapy] in terms of local control and survival against toxicities,” Dr. Kunkler said in an interview.

Omitting radiotherapy could help women avoid complications such as fatigue, changes to lung function, and an increased risk of cardiovascular damage.

“We think that these results should provide some reassurance that the omission of radiotherapy could be an option,” Dr. Kunkler said.
 

PRIME-2 results

The PRIME-2 study was a randomized trial that recruited 1,326 women with histologically confirmed, unilateral invasive breast cancer who were all 65 years or older.

For inclusion, the women had to have a tumor measuring 3 cm or less, have no nodal involvement, and be about to undergo breast-conserving surgery. Women also needed to be HR+ and be treated with adjuvant endocrine therapy.

The women were randomized 1:1 to receive adjuvant whole-breast irradiation at a dosing schedule of 40-50 Gy in 15-25 fractions or no radiotherapy in addition to adjuvant endocrine therapy.

The primary endpoint was the recurrence of breast cancer in the same breast at 10 years. There was a significantly lower rate of ipsilateral recurrence with radiotherapy than without it, at 0.9% and 9.8%, respectively (P = .00008).

Similarly, the 10-year rate of regional recurrence was significantly lower in the radiotherapy arm than in the no-radiotherapy arm (0.5% vs. 2.3%, P = .014).

However, there was no significant difference in the radiotherapy and nonradiotherapy arms when it came to distant recurrence (3.6% vs. 1.9%, P = .07), contralateral recurrence (2.2% vs. 1.2%, P = .20), or new, non–breast cancer (8.7% vs. 10.2%, P = .41).

The overall survival estimate at 10 years was 80.4% in women who did not receive radiotherapy and 81.0% in those who did (P = .68). Rates of metastasis-free survival were also similar (98.1% vs. 96.4%, P = .28).

“Most of these women are dying from non–breast cancer causes, reflecting the impact of competitive causes of non–breast cancer mortality,” Dr. Kunkler said.
 

Implications for practice

The current findings build on prior findings from the PRIME-2 study 5 years ago, which showed a small benefit of postoperative radiotherapy over no radiotherapy in reducing the rate of local recurrence. This led to the recommendation that postoperative radiotherapy might be safely omitted in some older women and influenced U.K. practice.

Indeed, Dr. Kunkler observed that U.K. guidelines have pretty much adopted the entry criteria for the PRIME-2 study (HR+, axillary node-negative [N0], T1–T2 up to 3 cm at the longest dimension, and clear margins) for the omission of radiotherapy.

“It’s had much less impact in the United States, where the usage of radiotherapy after breast-conserving surgery still remains very high,” Dr. Kunkler said.

He acknowledged that the current U.S. guidelines include the omission of radiotherapy in older women, but only those with much smaller (T1, N0) tumors, based on the findings of the Cancer and Leukemia Group B (CALGB) 9343 study.

“The findings from PRIME-2 so far seem consistent with long-term findings from CALGB 9343,” Matthew Katz, MD, of Lowell (Mass.) General Hospital Cancer Center, said in an interview.

SOURCE: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.

Skipping whole-breast adjuvant radiotherapy does not appear to affect long-term survival in women age 65 and older who have had surgery for early-stage, hormone receptor–positive (HR+) breast cancer, according to 10-year follow-up of the phase 3 PRIME-2 study.

Although the risk for local recurrence was higher among patients who did not receive radiotherapy, the absolute risk for recurrence was still low, said study investigator Ian Kunkler, MRCPUK, FRCR, of Western General Hospital, University of Edinburgh in Scotland.

Dr. Kunkler presented results from PRIME-2 at the 2020 San Antonio Breast Cancer Symposium.

“In older patients, we have to carefully balance benefits [of radiotherapy] in terms of local control and survival against toxicities,” Dr. Kunkler said in an interview.

Omitting radiotherapy could help women avoid complications such as fatigue, changes to lung function, and an increased risk of cardiovascular damage.

“We think that these results should provide some reassurance that the omission of radiotherapy could be an option,” Dr. Kunkler said.
 

PRIME-2 results

The PRIME-2 study was a randomized trial that recruited 1,326 women with histologically confirmed, unilateral invasive breast cancer who were all 65 years or older.

For inclusion, the women had to have a tumor measuring 3 cm or less, have no nodal involvement, and be about to undergo breast-conserving surgery. Women also needed to be HR+ and be treated with adjuvant endocrine therapy.

The women were randomized 1:1 to receive adjuvant whole-breast irradiation at a dosing schedule of 40-50 Gy in 15-25 fractions or no radiotherapy in addition to adjuvant endocrine therapy.

The primary endpoint was the recurrence of breast cancer in the same breast at 10 years. There was a significantly lower rate of ipsilateral recurrence with radiotherapy than without it, at 0.9% and 9.8%, respectively (P = .00008).

Similarly, the 10-year rate of regional recurrence was significantly lower in the radiotherapy arm than in the no-radiotherapy arm (0.5% vs. 2.3%, P = .014).

However, there was no significant difference in the radiotherapy and nonradiotherapy arms when it came to distant recurrence (3.6% vs. 1.9%, P = .07), contralateral recurrence (2.2% vs. 1.2%, P = .20), or new, non–breast cancer (8.7% vs. 10.2%, P = .41).

The overall survival estimate at 10 years was 80.4% in women who did not receive radiotherapy and 81.0% in those who did (P = .68). Rates of metastasis-free survival were also similar (98.1% vs. 96.4%, P = .28).

“Most of these women are dying from non–breast cancer causes, reflecting the impact of competitive causes of non–breast cancer mortality,” Dr. Kunkler said.
 

Implications for practice

The current findings build on prior findings from the PRIME-2 study 5 years ago, which showed a small benefit of postoperative radiotherapy over no radiotherapy in reducing the rate of local recurrence. This led to the recommendation that postoperative radiotherapy might be safely omitted in some older women and influenced U.K. practice.

Indeed, Dr. Kunkler observed that U.K. guidelines have pretty much adopted the entry criteria for the PRIME-2 study (HR+, axillary node-negative [N0], T1–T2 up to 3 cm at the longest dimension, and clear margins) for the omission of radiotherapy.

“It’s had much less impact in the United States, where the usage of radiotherapy after breast-conserving surgery still remains very high,” Dr. Kunkler said.

He acknowledged that the current U.S. guidelines include the omission of radiotherapy in older women, but only those with much smaller (T1, N0) tumors, based on the findings of the Cancer and Leukemia Group B (CALGB) 9343 study.

“The findings from PRIME-2 so far seem consistent with long-term findings from CALGB 9343,” Matthew Katz, MD, of Lowell (Mass.) General Hospital Cancer Center, said in an interview.

SOURCE: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.

A new monoclonal antibody that targets HER2 in breast cancer, margetuximab-cmkb (Margenza), has been approved by the Food and Drug Administration.

The new drug is indicated for use in combination with chemotherapy for the treatment of patients with metastatic HER2-positive breast cancer who have already received two or more prior anti-HER2 regimens, with at least one for metastatic disease.

Margetuximab-cmkb is also the first HER2-targeted therapy shown to improve progression-free survival (PFS) as compared with the first-ever HER2-targeted agent, trastuzumab in a head-to-head, phase 3 clinical trial (known as SOPHIA).

“Early detection and treatment have had a positive impact on the survival of patients with breast cancer, but the prognosis for people diagnosed with metastatic breast cancer remains poor, and additional treatments are needed,” said Hope S. Rugo, MD, director of breast oncology and clinical trials education, University of California, San Francisco, Diller Family Comprehensive Cancer Center, in a press release.

“As the only HER2-targeted agent to have shown a PFS improvement versus trastuzumab in a head-to-head phase 3 clinical trial, margetuximab with chemotherapy represents the newest treatment option for patients who have progressed on available HER2-directed therapies,” said Dr. Rugo, who is an investigator in the SOPHIA trial.

Like trastuzumab, margetuximab-cmkb binds HER2 with high specificity and affinity and disrupts signaling that drives cell proliferation and survival, but margetuximab binds with elevated affinity to both the lower- and higher-affinity forms of CD16A, an Fc gamma receptor important for antibody dependent cell-mediated cytotoxicity against tumor cells, according to the manufacturer, MacroGenics.
 

Details of the pivotal trial

The SOPHIA trial was a randomized, open-label, phase 3 clinical trial that compared margetuximab-cmkb plus chemotherapy with trastuzumab plus chemotherapy in both arms in patients with HER2-positive metastatic breast cancer who had previously been treated with anti–HER2-targeted therapies.

All patients in the cohort had previously received trastuzumab, all but one patient had previously also received pertuzumab, and most of the patients (91%) had also been treated with ado-trastuzumab emtansine, or T-DM1.

The trial randomly assigned 536 patients to receive either margetuximab-cmkb (n = 266) given intravenously at 15 mg/kg every 3 weeks or trastuzumab (n = 270) given intravenously at 6 mg/kg (or 8 mg/kg for loading dose) every 3 weeks in combination with either capecitabine, eribulin, gemcitabine, or vinorelbine, given at the standard doses.

As compared with trastuzumab, margetuximab plus chemotherapy led to a significant 24% reduction in the risk for progression or death (hazard ratio, 0.76).

The median PFS also favored margetuximab (5.8 months vs. 4.9 months), as did the overall response rate (22% vs. 16%).

The final overall survival analysis is expected in the second half of 2021.

Common adverse events associated with the margetuximab regimen included fatigue/asthenia (57%), nausea (33%), diarrhea (25%), and vomiting (21%). Infusion-related reactions occurred in 13% of patients receiving margetuximab, and almost all were grade 1 or 2, with only 1.5% at grade 3.

The product also carries a boxed warning for left ventricular dysfunction and embryo-fetal toxicity.

A version of this article first appeared on Medscape.com.

A new monoclonal antibody that targets HER2 in breast cancer, margetuximab-cmkb (Margenza), has been approved by the Food and Drug Administration.

The new drug is indicated for use in combination with chemotherapy for the treatment of patients with metastatic HER2-positive breast cancer who have already received two or more prior anti-HER2 regimens, with at least one for metastatic disease.

Margetuximab-cmkb is also the first HER2-targeted therapy shown to improve progression-free survival (PFS) as compared with the first-ever HER2-targeted agent, trastuzumab in a head-to-head, phase 3 clinical trial (known as SOPHIA).

“Early detection and treatment have had a positive impact on the survival of patients with breast cancer, but the prognosis for people diagnosed with metastatic breast cancer remains poor, and additional treatments are needed,” said Hope S. Rugo, MD, director of breast oncology and clinical trials education, University of California, San Francisco, Diller Family Comprehensive Cancer Center, in a press release.

“As the only HER2-targeted agent to have shown a PFS improvement versus trastuzumab in a head-to-head phase 3 clinical trial, margetuximab with chemotherapy represents the newest treatment option for patients who have progressed on available HER2-directed therapies,” said Dr. Rugo, who is an investigator in the SOPHIA trial.

Like trastuzumab, margetuximab-cmkb binds HER2 with high specificity and affinity and disrupts signaling that drives cell proliferation and survival, but margetuximab binds with elevated affinity to both the lower- and higher-affinity forms of CD16A, an Fc gamma receptor important for antibody dependent cell-mediated cytotoxicity against tumor cells, according to the manufacturer, MacroGenics.
 

Details of the pivotal trial

The SOPHIA trial was a randomized, open-label, phase 3 clinical trial that compared margetuximab-cmkb plus chemotherapy with trastuzumab plus chemotherapy in both arms in patients with HER2-positive metastatic breast cancer who had previously been treated with anti–HER2-targeted therapies.

All patients in the cohort had previously received trastuzumab, all but one patient had previously also received pertuzumab, and most of the patients (91%) had also been treated with ado-trastuzumab emtansine, or T-DM1.

The trial randomly assigned 536 patients to receive either margetuximab-cmkb (n = 266) given intravenously at 15 mg/kg every 3 weeks or trastuzumab (n = 270) given intravenously at 6 mg/kg (or 8 mg/kg for loading dose) every 3 weeks in combination with either capecitabine, eribulin, gemcitabine, or vinorelbine, given at the standard doses.

As compared with trastuzumab, margetuximab plus chemotherapy led to a significant 24% reduction in the risk for progression or death (hazard ratio, 0.76).

The median PFS also favored margetuximab (5.8 months vs. 4.9 months), as did the overall response rate (22% vs. 16%).

The final overall survival analysis is expected in the second half of 2021.

Common adverse events associated with the margetuximab regimen included fatigue/asthenia (57%), nausea (33%), diarrhea (25%), and vomiting (21%). Infusion-related reactions occurred in 13% of patients receiving margetuximab, and almost all were grade 1 or 2, with only 1.5% at grade 3.

The product also carries a boxed warning for left ventricular dysfunction and embryo-fetal toxicity.

A version of this article first appeared on Medscape.com.

A new monoclonal antibody that targets HER2 in breast cancer, margetuximab-cmkb (Margenza), has been approved by the Food and Drug Administration.

The new drug is indicated for use in combination with chemotherapy for the treatment of patients with metastatic HER2-positive breast cancer who have already received two or more prior anti-HER2 regimens, with at least one for metastatic disease.

Margetuximab-cmkb is also the first HER2-targeted therapy shown to improve progression-free survival (PFS) as compared with the first-ever HER2-targeted agent, trastuzumab in a head-to-head, phase 3 clinical trial (known as SOPHIA).

“Early detection and treatment have had a positive impact on the survival of patients with breast cancer, but the prognosis for people diagnosed with metastatic breast cancer remains poor, and additional treatments are needed,” said Hope S. Rugo, MD, director of breast oncology and clinical trials education, University of California, San Francisco, Diller Family Comprehensive Cancer Center, in a press release.

“As the only HER2-targeted agent to have shown a PFS improvement versus trastuzumab in a head-to-head phase 3 clinical trial, margetuximab with chemotherapy represents the newest treatment option for patients who have progressed on available HER2-directed therapies,” said Dr. Rugo, who is an investigator in the SOPHIA trial.

Like trastuzumab, margetuximab-cmkb binds HER2 with high specificity and affinity and disrupts signaling that drives cell proliferation and survival, but margetuximab binds with elevated affinity to both the lower- and higher-affinity forms of CD16A, an Fc gamma receptor important for antibody dependent cell-mediated cytotoxicity against tumor cells, according to the manufacturer, MacroGenics.
 

Details of the pivotal trial

The SOPHIA trial was a randomized, open-label, phase 3 clinical trial that compared margetuximab-cmkb plus chemotherapy with trastuzumab plus chemotherapy in both arms in patients with HER2-positive metastatic breast cancer who had previously been treated with anti–HER2-targeted therapies.

All patients in the cohort had previously received trastuzumab, all but one patient had previously also received pertuzumab, and most of the patients (91%) had also been treated with ado-trastuzumab emtansine, or T-DM1.

The trial randomly assigned 536 patients to receive either margetuximab-cmkb (n = 266) given intravenously at 15 mg/kg every 3 weeks or trastuzumab (n = 270) given intravenously at 6 mg/kg (or 8 mg/kg for loading dose) every 3 weeks in combination with either capecitabine, eribulin, gemcitabine, or vinorelbine, given at the standard doses.

As compared with trastuzumab, margetuximab plus chemotherapy led to a significant 24% reduction in the risk for progression or death (hazard ratio, 0.76).

The median PFS also favored margetuximab (5.8 months vs. 4.9 months), as did the overall response rate (22% vs. 16%).

The final overall survival analysis is expected in the second half of 2021.

Common adverse events associated with the margetuximab regimen included fatigue/asthenia (57%), nausea (33%), diarrhea (25%), and vomiting (21%). Infusion-related reactions occurred in 13% of patients receiving margetuximab, and almost all were grade 1 or 2, with only 1.5% at grade 3.

The product also carries a boxed warning for left ventricular dysfunction and embryo-fetal toxicity.

A version of this article first appeared on Medscape.com.