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In NSCLC, delayed chemo yields survival benefit comparable to early chemo
Patients with non–small-cell lung cancer (NSCLC) for whom adjuvant chemotherapy must be delayed for as long as 18 weeks have mortality outcomes that are no worse than those of patients who start chemotherapy soon after surgery, and those who undergo delayed chemotherapy have a significantly lower risk for death than patients who have no chemotherapy at all, investigators report.
A retrospective review of data on 12,473 patients with previously untreated NSCLC showed that there were no significant differences in 5-year overall survival (OS) estimates among patients who started multi-agent chemotherapy at 18-38 days postoperatively, from 39 to 56 days after surgery (the reference interval), or from 57 to 127 days after surgery, reported Daniel J. Boffa, MD, of Yale University, New Haven, Conn., and his colleagues.
In addition, when they used propensity score matching to pair patients who received chemotherapy with patients who did not undergo chemotherapy, they found that even late chemotherapy was associated with a significantly lower risk for death.
“Clinicians should still consider chemotherapy in appropriately selected patients that are healthy enough to tolerate it, up to 4 months after NSCLC resection. Further study is warranted to confirm these findings,” the investigators concluded (JAMA Oncol. 2017 Jan. 5 doi: 10.1001/jamaoncol.2016.5829).
In the retrospective review of records from the National Cancer Database, the investigators limited the study to patients for whom chemotherapy is typically prescribed: those with lymph node metastases, tumors 4 cm or larger, and/or local extension of disease. They looked at the association between the time to initiation of adjuvant chemotherapy and survival using Cox modeling with restricted cubic splines, a validated statistical method for evaluating links between survival and independent variables.
Dr. Boffa and his associates found that the unadjusted Kaplan-Meier 5-year OS estimates did not differ between the groups, at 53% for the early chemotherapy group (hazard ratio [HR] vs. the reference group, 1.009, P = .79), 55% for the reference group, and 53% for the later chemotherapy group (HR 1.037, P = .27).
Comparing adjuvant chemotherapy timing on the efficacy of surgery alone in patients matched by tumor stage and other features, the researchers found that chemotherapy started during any of the three intervals was associated with an approximately 34% reduction in risk of death compared with no chemotherapy (HR for the respective time intervals 0.672, 0.645, and 0.664; P less than .001 for each comparison).
The study helps to clarify for clinicians the benefits of adjuvant chemotherapy in select patients with NSCLC in a real-world setting, Howard (Jack) West, MD, of the Swedish Cancer Institute, Seattle, said in an accompanying editorial (JAMA Oncol. 2017 Jan. 5 doi: 10.1001/jamaoncol.2016.5798).
“While retrospective data cannot define the benefit of delayed adjuvant chemotherapy with the clarity of a prospective randomized trial, we must remember that in the land of the blind, the one-eyed man is king; these limited data inject an evidence-based answer for a very common clinical question for which we have been forced by necessity to rely only on our best judgments,” he wrote.
The study was internally supported. The authors and Dr. West reported no conflict of interest disclosures.
Patients with non–small-cell lung cancer (NSCLC) for whom adjuvant chemotherapy must be delayed for as long as 18 weeks have mortality outcomes that are no worse than those of patients who start chemotherapy soon after surgery, and those who undergo delayed chemotherapy have a significantly lower risk for death than patients who have no chemotherapy at all, investigators report.
A retrospective review of data on 12,473 patients with previously untreated NSCLC showed that there were no significant differences in 5-year overall survival (OS) estimates among patients who started multi-agent chemotherapy at 18-38 days postoperatively, from 39 to 56 days after surgery (the reference interval), or from 57 to 127 days after surgery, reported Daniel J. Boffa, MD, of Yale University, New Haven, Conn., and his colleagues.
In addition, when they used propensity score matching to pair patients who received chemotherapy with patients who did not undergo chemotherapy, they found that even late chemotherapy was associated with a significantly lower risk for death.
“Clinicians should still consider chemotherapy in appropriately selected patients that are healthy enough to tolerate it, up to 4 months after NSCLC resection. Further study is warranted to confirm these findings,” the investigators concluded (JAMA Oncol. 2017 Jan. 5 doi: 10.1001/jamaoncol.2016.5829).
In the retrospective review of records from the National Cancer Database, the investigators limited the study to patients for whom chemotherapy is typically prescribed: those with lymph node metastases, tumors 4 cm or larger, and/or local extension of disease. They looked at the association between the time to initiation of adjuvant chemotherapy and survival using Cox modeling with restricted cubic splines, a validated statistical method for evaluating links between survival and independent variables.
Dr. Boffa and his associates found that the unadjusted Kaplan-Meier 5-year OS estimates did not differ between the groups, at 53% for the early chemotherapy group (hazard ratio [HR] vs. the reference group, 1.009, P = .79), 55% for the reference group, and 53% for the later chemotherapy group (HR 1.037, P = .27).
Comparing adjuvant chemotherapy timing on the efficacy of surgery alone in patients matched by tumor stage and other features, the researchers found that chemotherapy started during any of the three intervals was associated with an approximately 34% reduction in risk of death compared with no chemotherapy (HR for the respective time intervals 0.672, 0.645, and 0.664; P less than .001 for each comparison).
The study helps to clarify for clinicians the benefits of adjuvant chemotherapy in select patients with NSCLC in a real-world setting, Howard (Jack) West, MD, of the Swedish Cancer Institute, Seattle, said in an accompanying editorial (JAMA Oncol. 2017 Jan. 5 doi: 10.1001/jamaoncol.2016.5798).
“While retrospective data cannot define the benefit of delayed adjuvant chemotherapy with the clarity of a prospective randomized trial, we must remember that in the land of the blind, the one-eyed man is king; these limited data inject an evidence-based answer for a very common clinical question for which we have been forced by necessity to rely only on our best judgments,” he wrote.
The study was internally supported. The authors and Dr. West reported no conflict of interest disclosures.
Patients with non–small-cell lung cancer (NSCLC) for whom adjuvant chemotherapy must be delayed for as long as 18 weeks have mortality outcomes that are no worse than those of patients who start chemotherapy soon after surgery, and those who undergo delayed chemotherapy have a significantly lower risk for death than patients who have no chemotherapy at all, investigators report.
A retrospective review of data on 12,473 patients with previously untreated NSCLC showed that there were no significant differences in 5-year overall survival (OS) estimates among patients who started multi-agent chemotherapy at 18-38 days postoperatively, from 39 to 56 days after surgery (the reference interval), or from 57 to 127 days after surgery, reported Daniel J. Boffa, MD, of Yale University, New Haven, Conn., and his colleagues.
In addition, when they used propensity score matching to pair patients who received chemotherapy with patients who did not undergo chemotherapy, they found that even late chemotherapy was associated with a significantly lower risk for death.
“Clinicians should still consider chemotherapy in appropriately selected patients that are healthy enough to tolerate it, up to 4 months after NSCLC resection. Further study is warranted to confirm these findings,” the investigators concluded (JAMA Oncol. 2017 Jan. 5 doi: 10.1001/jamaoncol.2016.5829).
In the retrospective review of records from the National Cancer Database, the investigators limited the study to patients for whom chemotherapy is typically prescribed: those with lymph node metastases, tumors 4 cm or larger, and/or local extension of disease. They looked at the association between the time to initiation of adjuvant chemotherapy and survival using Cox modeling with restricted cubic splines, a validated statistical method for evaluating links between survival and independent variables.
Dr. Boffa and his associates found that the unadjusted Kaplan-Meier 5-year OS estimates did not differ between the groups, at 53% for the early chemotherapy group (hazard ratio [HR] vs. the reference group, 1.009, P = .79), 55% for the reference group, and 53% for the later chemotherapy group (HR 1.037, P = .27).
Comparing adjuvant chemotherapy timing on the efficacy of surgery alone in patients matched by tumor stage and other features, the researchers found that chemotherapy started during any of the three intervals was associated with an approximately 34% reduction in risk of death compared with no chemotherapy (HR for the respective time intervals 0.672, 0.645, and 0.664; P less than .001 for each comparison).
The study helps to clarify for clinicians the benefits of adjuvant chemotherapy in select patients with NSCLC in a real-world setting, Howard (Jack) West, MD, of the Swedish Cancer Institute, Seattle, said in an accompanying editorial (JAMA Oncol. 2017 Jan. 5 doi: 10.1001/jamaoncol.2016.5798).
“While retrospective data cannot define the benefit of delayed adjuvant chemotherapy with the clarity of a prospective randomized trial, we must remember that in the land of the blind, the one-eyed man is king; these limited data inject an evidence-based answer for a very common clinical question for which we have been forced by necessity to rely only on our best judgments,” he wrote.
The study was internally supported. The authors and Dr. West reported no conflict of interest disclosures.
FROM JAMA ONCOLOGY
Key clinical point: Chemotherapy delayed for up to 18 weeks after surgery offers survival benefits comparable to those of earlier chemotherapy in non–small-cell lung cancer.
Major finding: There were no statistical differences in 5-year survival of patients with NSCLC started on chemotherapy either 18-38, 39-56, or 57-127 days after surgery.
Data source: Retrospective observational study of 12,473 patients with untreated NSCLC in the National Cancer Database.
Disclosures: The study was internally supported. The authors and Dr. West reported no conflict of interest disclosures.
Confirmation CT prevents unnecessary pulmonary nodule bronchoscopy
It’s probably a good idea to do a repeat CT the morning of a scheduled bronchoscopy to make sure the pulmonary nodule is still there, according to investigators from Johns Hopkins University, Baltimore.
From Jan. 2015 to June 2016, 116 patients there were scheduled for navigational bronchoscopy to diagnose pulmonary lesions found on screening CTs. Eight (6.9%) – four men, four women, with an average age of 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellations of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For canceled cases, the average time from screening CT to scheduled bronchoscopy was 53 days; for patients who underwent a bronchoscopy, it was 50 days (Ann Am Thorac Soc. 2016 Dec;13[12]:2223-8).
It can take months to schedule a bronchoscopy after a pulmonary nodule is found on CT screening. Once in a while, the investigators and others have found, even suspicious nodules resolve on their own, and patients end up having a bronchoscopy they don’t need.
“If there is a significant delay from the initial imaging, practitioners should consider repeat studies before proceeding with the scheduled procedure ... Same-day imaging may decrease unnecessary procedural risk ... The optimal time that should be allowed to pass is difficult to ascertain,” said investigators led by Roy Semaan, MD, of the division of pulmonary and critical care medicine at Hopkins.
The team used a newer version of electromagnetic navigation bronchoscopy (Veran Medical Technologies, St. Louis), which requires expiratory and inspiratory CTs the morning of the procedure so software can build a virtual airway model to localize the nodule.
In addition to nodule resolution, same-day CTs might identify disease progression that alters the diagnostic plan of care.
“The most obvious risk associated with repeat CT imaging is the increased radiation exposure to the patient. Patients in our study who received inspiratory and expiratory CT scans ... had a mean exposure of 9.485 mSv, which is not “negligible, but one-time doses at this range are generally considered to be low risk for contributing to the future development of a malignancy,” the team said.
The extra cost of a same-day noncontrast chest CT – about $300, the authors said – is more than offset if it cancels “an unnecessary procedure with its associated risks,” they said.
Dr. Semaan had no disclosures. Three investigators reported grants and personal fees from Veran.
It’s probably a good idea to do a repeat CT the morning of a scheduled bronchoscopy to make sure the pulmonary nodule is still there, according to investigators from Johns Hopkins University, Baltimore.
From Jan. 2015 to June 2016, 116 patients there were scheduled for navigational bronchoscopy to diagnose pulmonary lesions found on screening CTs. Eight (6.9%) – four men, four women, with an average age of 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellations of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For canceled cases, the average time from screening CT to scheduled bronchoscopy was 53 days; for patients who underwent a bronchoscopy, it was 50 days (Ann Am Thorac Soc. 2016 Dec;13[12]:2223-8).
It can take months to schedule a bronchoscopy after a pulmonary nodule is found on CT screening. Once in a while, the investigators and others have found, even suspicious nodules resolve on their own, and patients end up having a bronchoscopy they don’t need.
“If there is a significant delay from the initial imaging, practitioners should consider repeat studies before proceeding with the scheduled procedure ... Same-day imaging may decrease unnecessary procedural risk ... The optimal time that should be allowed to pass is difficult to ascertain,” said investigators led by Roy Semaan, MD, of the division of pulmonary and critical care medicine at Hopkins.
The team used a newer version of electromagnetic navigation bronchoscopy (Veran Medical Technologies, St. Louis), which requires expiratory and inspiratory CTs the morning of the procedure so software can build a virtual airway model to localize the nodule.
In addition to nodule resolution, same-day CTs might identify disease progression that alters the diagnostic plan of care.
“The most obvious risk associated with repeat CT imaging is the increased radiation exposure to the patient. Patients in our study who received inspiratory and expiratory CT scans ... had a mean exposure of 9.485 mSv, which is not “negligible, but one-time doses at this range are generally considered to be low risk for contributing to the future development of a malignancy,” the team said.
The extra cost of a same-day noncontrast chest CT – about $300, the authors said – is more than offset if it cancels “an unnecessary procedure with its associated risks,” they said.
Dr. Semaan had no disclosures. Three investigators reported grants and personal fees from Veran.
It’s probably a good idea to do a repeat CT the morning of a scheduled bronchoscopy to make sure the pulmonary nodule is still there, according to investigators from Johns Hopkins University, Baltimore.
From Jan. 2015 to June 2016, 116 patients there were scheduled for navigational bronchoscopy to diagnose pulmonary lesions found on screening CTs. Eight (6.9%) – four men, four women, with an average age of 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellations of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For canceled cases, the average time from screening CT to scheduled bronchoscopy was 53 days; for patients who underwent a bronchoscopy, it was 50 days (Ann Am Thorac Soc. 2016 Dec;13[12]:2223-8).
It can take months to schedule a bronchoscopy after a pulmonary nodule is found on CT screening. Once in a while, the investigators and others have found, even suspicious nodules resolve on their own, and patients end up having a bronchoscopy they don’t need.
“If there is a significant delay from the initial imaging, practitioners should consider repeat studies before proceeding with the scheduled procedure ... Same-day imaging may decrease unnecessary procedural risk ... The optimal time that should be allowed to pass is difficult to ascertain,” said investigators led by Roy Semaan, MD, of the division of pulmonary and critical care medicine at Hopkins.
The team used a newer version of electromagnetic navigation bronchoscopy (Veran Medical Technologies, St. Louis), which requires expiratory and inspiratory CTs the morning of the procedure so software can build a virtual airway model to localize the nodule.
In addition to nodule resolution, same-day CTs might identify disease progression that alters the diagnostic plan of care.
“The most obvious risk associated with repeat CT imaging is the increased radiation exposure to the patient. Patients in our study who received inspiratory and expiratory CT scans ... had a mean exposure of 9.485 mSv, which is not “negligible, but one-time doses at this range are generally considered to be low risk for contributing to the future development of a malignancy,” the team said.
The extra cost of a same-day noncontrast chest CT – about $300, the authors said – is more than offset if it cancels “an unnecessary procedure with its associated risks,” they said.
Dr. Semaan had no disclosures. Three investigators reported grants and personal fees from Veran.
Key clinical point:
Major finding: Of 116 patients, eight (6.9%) – four men, four women, average age 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellation of their procedure.
Data source: Prospective series from Johns Hopkins University.
Disclosures: Three investigators reported grants and personal fees from Veran.
Paraneoplastic Isaacs syndrome leading to diagnosis of small-cell lung cancer
Paraneoplastic Isaacs syndrome is a rare disorder with distinct clinical and electromyographic characteristics. It is a consequence of neoplastic process that is not directly caused by the tumor itself, but usually mediated by immune response primarily against the tumor and neural tissues are damaged owing to bystander effect. Paraneoplastic neurologic disorders may precede cancer diagnosis. Here we report the case of 75-year-old woman who presented with numbness, tingling sensation, and weakness of lower extremities, and was diagnosed with Isaacs syndrome and subsequently small-cell lung cancer. Plasmapheresis and treatment of small-cell lung cancer produced signficant symptoms improvement. We also conduct a complete review of the published case reports and case series of Isaacs syndrome of paraneoplastic etiology, which usually has good response to carbamazepine and to specfic treatment of underlying neoplasm.
Click on the PDF icon at the top of this introduction to read the full article.
Paraneoplastic Isaacs syndrome is a rare disorder with distinct clinical and electromyographic characteristics. It is a consequence of neoplastic process that is not directly caused by the tumor itself, but usually mediated by immune response primarily against the tumor and neural tissues are damaged owing to bystander effect. Paraneoplastic neurologic disorders may precede cancer diagnosis. Here we report the case of 75-year-old woman who presented with numbness, tingling sensation, and weakness of lower extremities, and was diagnosed with Isaacs syndrome and subsequently small-cell lung cancer. Plasmapheresis and treatment of small-cell lung cancer produced signficant symptoms improvement. We also conduct a complete review of the published case reports and case series of Isaacs syndrome of paraneoplastic etiology, which usually has good response to carbamazepine and to specfic treatment of underlying neoplasm.
Click on the PDF icon at the top of this introduction to read the full article.
Paraneoplastic Isaacs syndrome is a rare disorder with distinct clinical and electromyographic characteristics. It is a consequence of neoplastic process that is not directly caused by the tumor itself, but usually mediated by immune response primarily against the tumor and neural tissues are damaged owing to bystander effect. Paraneoplastic neurologic disorders may precede cancer diagnosis. Here we report the case of 75-year-old woman who presented with numbness, tingling sensation, and weakness of lower extremities, and was diagnosed with Isaacs syndrome and subsequently small-cell lung cancer. Plasmapheresis and treatment of small-cell lung cancer produced signficant symptoms improvement. We also conduct a complete review of the published case reports and case series of Isaacs syndrome of paraneoplastic etiology, which usually has good response to carbamazepine and to specfic treatment of underlying neoplasm.
Click on the PDF icon at the top of this introduction to read the full article.
Quality of life after surgery for pleural malignant mesothelioma – methodological considerations
Background There is a dearth of literature on patient quality of life (QoL) after treatment for malignant pleural mesothelioma (MPM).
Objectives To review the literature on QoL after surgery for MPM and assess differences in quality of life between patients who have extrapleural pneumonectomy (EPP) and those who have pleurectomy and decortication (P-D).
Methods We retrieved and reviewed original research studies on quality of life after mesothelioma surgery. They had been published from January 1990 through June 2016, and included 15 articles and 12 datasets for a total of 523 patients.
Results QoL data was available for 102 EPP patients and 296 P-D patients. Two studies directly compared QoL outcomes between the 2 techniques. Symptoms, lung function parameters, and physical and social functioning were still compromised 6 months after surgery. However, P-D patients fared better than did EPP patients across QoL measures.
Limitations The amount of available literature is small, and the studies are heterogeneous.
Conclusions QoL is better for a longer period of time in patients who undergo P-D, compared with those who have EPP. Given the need for multimodality therapy for MPM and the aggressive nature of the disease, QoL outcomes should be strongly considered when choosing type of surgery for mesothelioma.
Click on the PDF icon at the top of this introduction to read the full article.
Background There is a dearth of literature on patient quality of life (QoL) after treatment for malignant pleural mesothelioma (MPM).
Objectives To review the literature on QoL after surgery for MPM and assess differences in quality of life between patients who have extrapleural pneumonectomy (EPP) and those who have pleurectomy and decortication (P-D).
Methods We retrieved and reviewed original research studies on quality of life after mesothelioma surgery. They had been published from January 1990 through June 2016, and included 15 articles and 12 datasets for a total of 523 patients.
Results QoL data was available for 102 EPP patients and 296 P-D patients. Two studies directly compared QoL outcomes between the 2 techniques. Symptoms, lung function parameters, and physical and social functioning were still compromised 6 months after surgery. However, P-D patients fared better than did EPP patients across QoL measures.
Limitations The amount of available literature is small, and the studies are heterogeneous.
Conclusions QoL is better for a longer period of time in patients who undergo P-D, compared with those who have EPP. Given the need for multimodality therapy for MPM and the aggressive nature of the disease, QoL outcomes should be strongly considered when choosing type of surgery for mesothelioma.
Click on the PDF icon at the top of this introduction to read the full article.
Background There is a dearth of literature on patient quality of life (QoL) after treatment for malignant pleural mesothelioma (MPM).
Objectives To review the literature on QoL after surgery for MPM and assess differences in quality of life between patients who have extrapleural pneumonectomy (EPP) and those who have pleurectomy and decortication (P-D).
Methods We retrieved and reviewed original research studies on quality of life after mesothelioma surgery. They had been published from January 1990 through June 2016, and included 15 articles and 12 datasets for a total of 523 patients.
Results QoL data was available for 102 EPP patients and 296 P-D patients. Two studies directly compared QoL outcomes between the 2 techniques. Symptoms, lung function parameters, and physical and social functioning were still compromised 6 months after surgery. However, P-D patients fared better than did EPP patients across QoL measures.
Limitations The amount of available literature is small, and the studies are heterogeneous.
Conclusions QoL is better for a longer period of time in patients who undergo P-D, compared with those who have EPP. Given the need for multimodality therapy for MPM and the aggressive nature of the disease, QoL outcomes should be strongly considered when choosing type of surgery for mesothelioma.
Click on the PDF icon at the top of this introduction to read the full article.
Noncancerous disease has a significant impact on lung cancer surgery survival
After older patients undergo lung resection for stage I non–small-cell lung cancer, they are actually at greater risk of death from something other than lung cancer for up to 2.5 years, according to researchers at Memorial Sloan Kettering Cancer Center, New York. The findings were published online in the Journal of Clinical Oncology (2016;34: doi: 10.1200/JCO.2016.69.0834).
“As age increases, the risk of competing events increases, such as death from noncancer diseases,” wrote Takashi Eguchi, MD, and coauthors. “In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors – specifically, comorbidities associated with increasing age – contribute to the risk of death.”
The researchers examined outcomes in three different age groups: younger than 65, 65-74, and 75 and older. The study focused on 2,186 patients with pathologic stage I non–small-cell lung cancer (NSCLC) among a population of 5,371 consecutive patients who had resection for primary lung cancer from 2000 to 2011. Seventy percent of patients in the study group were 65 and older, and 29.2% were 75 and older.
In all age groups, the calculated 5-year cumulative incidence of death (CID) for lung cancer–specific causes exceeded that for noncancer causes, but at significant intervals the 65-and-over groups were more likely to die from the latter. For the overall study group, noncancer-specific causes accounted for a higher CID through 18 months after surgery, when the CID for both cancer and noncancer causes crossed at around 2.9. At 5 years, the overall lung cancer–specific CID was 10.4 vs. 5.3 for noncancer specific causes.
However, in the older age groups, those trends were more pronounced. In those aged 65-74, CID for both causes met at around 3.15 at 18 months (10.7 for lung cancer–specific and 4.9 for noncancer specific at 5 years), whereas for those 75 and older, CID for noncancer causes exceeded that for lung cancer–related causes for 2.5 years, when both were around 6; reaching 13.2 for lung cancer–specific and 9 for noncancer-specific at 5 years.
In the 65-and-younger group, lung cancer– and noncancer-specific CIDs were equal for about 3 months after surgery, when the lung cancer deaths tracked upward and the trends diverged (at 5 years, CID was 7.5 for lung cancer–specific and 1 for noncancer specific).
“We have shown that in patients with stage I NSCLC, the majority of postoperative severe morbidity, 1-year mortality, and 5-year noncancer-specific mortality were attributable to cardiorespiratory diseases,” Dr. Eguchi and colleagues said.
“We have also shown that short-term mortality is primarily attributable to noncancer-specific diseases.” The findings underscore the importance of screening older patients for noncancer-specific diseases that could alter outcomes, the researchers said.
Of the 2,186 stage I NSCLC patients in the study, 167 developed severe morbidities after surgery; 68.3% developed respiratory problems and 18.6% went on to develop cardiovascular problems. Patients who had lobectomy were more likely to develop respiratory problems than were those who had sublobar resection, Dr. Eguchi and coauthors said.
Respiratory and cardiovascular diseases were the most frequent causes of death early after surgery. At 30 days, respiratory disease accounted for 5 deaths and cardiovascular disease 7 of 15 total deaths at 30 days; and at 90 days, 11 and 7, respectively, of 27 overall deaths. Even at 1 year, noncancer issues were the leading cause of death (50%), followed by lung cancer–specific causes (27.8%) and other cancer specific disease (13.3%).
“Noncancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Dr. Eguchi and coauthors said. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.”
The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial disclosures.
Every surgeon performing lung resection comes across elderly patients who are at a higher risk than usual for a formal lung resection. In this era of screening and the abundant use of CT scans, this is increasingly common. Selection of the optimal treatment approach is often done intuitively, balancing the increased risk of surgery vs. the improved cancer-specific survival and the baseline life expectancy of the patient. This manuscript provides more quantitative estimates of this balance and draws attention, through a competing risks analysis, to the importance of non–cancer-related mortality in elderly patients.
The authors point out that non–cancer-related mortality is more common than cancer-related mortality for up to 2.5 years after surgery in patients greater than 75 years of age. This way of examining a situation is different from the usual emphasis on 30-day (and more recently the 90-day) perioperative mortality. The manuscript significantly adds to the decision-making framework of this increasingly important population and is a useful read for all lung cancer surgeons.
Sai Yendamuri, MD, is an attending surgeon in the department of thoracic surgery, the director, Thoracic Surgery Research Laboratory, and associate professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y. He is associate medical editor for Thoracic Surgery News.
Every surgeon performing lung resection comes across elderly patients who are at a higher risk than usual for a formal lung resection. In this era of screening and the abundant use of CT scans, this is increasingly common. Selection of the optimal treatment approach is often done intuitively, balancing the increased risk of surgery vs. the improved cancer-specific survival and the baseline life expectancy of the patient. This manuscript provides more quantitative estimates of this balance and draws attention, through a competing risks analysis, to the importance of non–cancer-related mortality in elderly patients.
The authors point out that non–cancer-related mortality is more common than cancer-related mortality for up to 2.5 years after surgery in patients greater than 75 years of age. This way of examining a situation is different from the usual emphasis on 30-day (and more recently the 90-day) perioperative mortality. The manuscript significantly adds to the decision-making framework of this increasingly important population and is a useful read for all lung cancer surgeons.
Sai Yendamuri, MD, is an attending surgeon in the department of thoracic surgery, the director, Thoracic Surgery Research Laboratory, and associate professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y. He is associate medical editor for Thoracic Surgery News.
Every surgeon performing lung resection comes across elderly patients who are at a higher risk than usual for a formal lung resection. In this era of screening and the abundant use of CT scans, this is increasingly common. Selection of the optimal treatment approach is often done intuitively, balancing the increased risk of surgery vs. the improved cancer-specific survival and the baseline life expectancy of the patient. This manuscript provides more quantitative estimates of this balance and draws attention, through a competing risks analysis, to the importance of non–cancer-related mortality in elderly patients.
The authors point out that non–cancer-related mortality is more common than cancer-related mortality for up to 2.5 years after surgery in patients greater than 75 years of age. This way of examining a situation is different from the usual emphasis on 30-day (and more recently the 90-day) perioperative mortality. The manuscript significantly adds to the decision-making framework of this increasingly important population and is a useful read for all lung cancer surgeons.
Sai Yendamuri, MD, is an attending surgeon in the department of thoracic surgery, the director, Thoracic Surgery Research Laboratory, and associate professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y. He is associate medical editor for Thoracic Surgery News.
After older patients undergo lung resection for stage I non–small-cell lung cancer, they are actually at greater risk of death from something other than lung cancer for up to 2.5 years, according to researchers at Memorial Sloan Kettering Cancer Center, New York. The findings were published online in the Journal of Clinical Oncology (2016;34: doi: 10.1200/JCO.2016.69.0834).
“As age increases, the risk of competing events increases, such as death from noncancer diseases,” wrote Takashi Eguchi, MD, and coauthors. “In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors – specifically, comorbidities associated with increasing age – contribute to the risk of death.”
The researchers examined outcomes in three different age groups: younger than 65, 65-74, and 75 and older. The study focused on 2,186 patients with pathologic stage I non–small-cell lung cancer (NSCLC) among a population of 5,371 consecutive patients who had resection for primary lung cancer from 2000 to 2011. Seventy percent of patients in the study group were 65 and older, and 29.2% were 75 and older.
In all age groups, the calculated 5-year cumulative incidence of death (CID) for lung cancer–specific causes exceeded that for noncancer causes, but at significant intervals the 65-and-over groups were more likely to die from the latter. For the overall study group, noncancer-specific causes accounted for a higher CID through 18 months after surgery, when the CID for both cancer and noncancer causes crossed at around 2.9. At 5 years, the overall lung cancer–specific CID was 10.4 vs. 5.3 for noncancer specific causes.
However, in the older age groups, those trends were more pronounced. In those aged 65-74, CID for both causes met at around 3.15 at 18 months (10.7 for lung cancer–specific and 4.9 for noncancer specific at 5 years), whereas for those 75 and older, CID for noncancer causes exceeded that for lung cancer–related causes for 2.5 years, when both were around 6; reaching 13.2 for lung cancer–specific and 9 for noncancer-specific at 5 years.
In the 65-and-younger group, lung cancer– and noncancer-specific CIDs were equal for about 3 months after surgery, when the lung cancer deaths tracked upward and the trends diverged (at 5 years, CID was 7.5 for lung cancer–specific and 1 for noncancer specific).
“We have shown that in patients with stage I NSCLC, the majority of postoperative severe morbidity, 1-year mortality, and 5-year noncancer-specific mortality were attributable to cardiorespiratory diseases,” Dr. Eguchi and colleagues said.
“We have also shown that short-term mortality is primarily attributable to noncancer-specific diseases.” The findings underscore the importance of screening older patients for noncancer-specific diseases that could alter outcomes, the researchers said.
Of the 2,186 stage I NSCLC patients in the study, 167 developed severe morbidities after surgery; 68.3% developed respiratory problems and 18.6% went on to develop cardiovascular problems. Patients who had lobectomy were more likely to develop respiratory problems than were those who had sublobar resection, Dr. Eguchi and coauthors said.
Respiratory and cardiovascular diseases were the most frequent causes of death early after surgery. At 30 days, respiratory disease accounted for 5 deaths and cardiovascular disease 7 of 15 total deaths at 30 days; and at 90 days, 11 and 7, respectively, of 27 overall deaths. Even at 1 year, noncancer issues were the leading cause of death (50%), followed by lung cancer–specific causes (27.8%) and other cancer specific disease (13.3%).
“Noncancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Dr. Eguchi and coauthors said. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.”
The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial disclosures.
After older patients undergo lung resection for stage I non–small-cell lung cancer, they are actually at greater risk of death from something other than lung cancer for up to 2.5 years, according to researchers at Memorial Sloan Kettering Cancer Center, New York. The findings were published online in the Journal of Clinical Oncology (2016;34: doi: 10.1200/JCO.2016.69.0834).
“As age increases, the risk of competing events increases, such as death from noncancer diseases,” wrote Takashi Eguchi, MD, and coauthors. “In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors – specifically, comorbidities associated with increasing age – contribute to the risk of death.”
The researchers examined outcomes in three different age groups: younger than 65, 65-74, and 75 and older. The study focused on 2,186 patients with pathologic stage I non–small-cell lung cancer (NSCLC) among a population of 5,371 consecutive patients who had resection for primary lung cancer from 2000 to 2011. Seventy percent of patients in the study group were 65 and older, and 29.2% were 75 and older.
In all age groups, the calculated 5-year cumulative incidence of death (CID) for lung cancer–specific causes exceeded that for noncancer causes, but at significant intervals the 65-and-over groups were more likely to die from the latter. For the overall study group, noncancer-specific causes accounted for a higher CID through 18 months after surgery, when the CID for both cancer and noncancer causes crossed at around 2.9. At 5 years, the overall lung cancer–specific CID was 10.4 vs. 5.3 for noncancer specific causes.
However, in the older age groups, those trends were more pronounced. In those aged 65-74, CID for both causes met at around 3.15 at 18 months (10.7 for lung cancer–specific and 4.9 for noncancer specific at 5 years), whereas for those 75 and older, CID for noncancer causes exceeded that for lung cancer–related causes for 2.5 years, when both were around 6; reaching 13.2 for lung cancer–specific and 9 for noncancer-specific at 5 years.
In the 65-and-younger group, lung cancer– and noncancer-specific CIDs were equal for about 3 months after surgery, when the lung cancer deaths tracked upward and the trends diverged (at 5 years, CID was 7.5 for lung cancer–specific and 1 for noncancer specific).
“We have shown that in patients with stage I NSCLC, the majority of postoperative severe morbidity, 1-year mortality, and 5-year noncancer-specific mortality were attributable to cardiorespiratory diseases,” Dr. Eguchi and colleagues said.
“We have also shown that short-term mortality is primarily attributable to noncancer-specific diseases.” The findings underscore the importance of screening older patients for noncancer-specific diseases that could alter outcomes, the researchers said.
Of the 2,186 stage I NSCLC patients in the study, 167 developed severe morbidities after surgery; 68.3% developed respiratory problems and 18.6% went on to develop cardiovascular problems. Patients who had lobectomy were more likely to develop respiratory problems than were those who had sublobar resection, Dr. Eguchi and coauthors said.
Respiratory and cardiovascular diseases were the most frequent causes of death early after surgery. At 30 days, respiratory disease accounted for 5 deaths and cardiovascular disease 7 of 15 total deaths at 30 days; and at 90 days, 11 and 7, respectively, of 27 overall deaths. Even at 1 year, noncancer issues were the leading cause of death (50%), followed by lung cancer–specific causes (27.8%) and other cancer specific disease (13.3%).
“Noncancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Dr. Eguchi and coauthors said. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.”
The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial disclosures.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Risk of non-cancer death after curative resection of stage 1 non–small-call lung cancer (NSCLC) exceeded that of lung-cancer deaths 1.5 to 2.5 years after surgery in older patients.
Major finding: In patients aged 75 and older the risk of non–lung-cancer–related death exceeded the risk of death from lung cancer for 2.5 years after surgery, whereas in patients 65 and younger the risk of non–lung cancer death exceeded that of lung-cancer death for 3 months after surgery.
Data Source: Single-center analysis of 5,371 consecutive patients who had curative lung cancer resection from 2000 to 2011, 2,186 of whom had stage 1 NSCLC.
Disclosures: The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial relationships to disclose.
VIDEO: Improved QOL an added benefit of pembrolizumab for NSCLC patients
VIENNA – Patients with metastatic non–small-cell lung cancer with high levels of PD-L1 who received first-line pembrolizumab treatment had clinically meaningful improvement in their quality of life, compared with patients randomized to chemotherapy, in a prespecified secondary analysis of data from the drug’s pivotal trial.
This boost in quality of life as well as other measures of health status add to the pivotal trial’s primary finding of significantly increased progression-free survival compared with chemotherapy, as well as previously-reported secondary findings of superior overall survival, objective response rate, and safety with pembrolizumab compared with chemotherapy (N Engl J Med. 2016 Nov 10;375[19]:1823-33), Julie R. Brahmer, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
The primary endpoint of the Study of Pembrolizumab Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non–Small Cell Lung Cancer (KEYNOTE-024) showed an average 4.3-month increase in progression-free survival with pembrolizumab immunotherapy, compared with a standard chemotherapy regimen.
Improved quality of life on top of improved efficacy and safety is an important added benefit from pembrolizumab that should further spur its widespread adoption as first-line treatment for approved patients, Dr. Brahmer said in a video interview.
“When you talk about improving efficacy by months, patients and physicians want to also see improved quality of life,” said Dr. Brahmer, director of thoracic oncology at the Johns Hopkins Kimmel Cancer Center in Baltimore. “If symptoms are not improved or there are a ton of side effects with the treatment then use might be low.”
Based on its performance in KEYNOTE-024, pembrolizumab (Keytruda) received Food and Drug Administration approval on Oct. 24, 2016, as first-line treatment for patients with metastatic non–small-cell lung cancer that has a tumor proportion score of at least 50% for programmed death ligand 1 (PD-L1). Pembrolizumab is a monoclonal antibody that binds and blocks PD-1, the immune-cell receptor that tumor-cell PD-L1 binds to make immune cells less active. Other new immune checkpoint inhibitor drugs that act by blocking PD-1 or PD-L1 have shown similar quality of life benefits, she noted.
Routine availability of pembrolizumab as initial treatment for patients who have tumors with this level of PD-L1 expression (and also have no EGFR or ALK genomic aberrations) is shifting practice, Dr. Brahmer said.
“It’s catching on. The limitation right now is making sure patients get tested” for their PD-L1 tumor proportion score at the time they are first diagnosed. “Medical oncologists need to educate pathologists that we need this testing automatically, upfront. It’s not there yet,” she said.
Patients also are enthused. “There is a lot of chemo-exhaustion among patients. They are looking for something different, and something that uses their immune system makes sense.” But only about one quarter of patients have tumors with this level of PD-L1 expression; the others must start chemotherapy first before trying immunotherapy, unless they have an EGFR mutation. Out-of-pocket cost for pembrolizumab is also a major issues for many patients, she said.
KEYNOTE-024 randomized 305 patients at 102 international sites and followed patients for a median of 11 months. Dr. Brahmer and her associates made two primary analyses of patient-reported outcomes. One was measurement of global health status at 15 weeks after the start of treatment using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire designed to assess quality of life. Weighted averaging of the EORTC QCQ-C30 scores showed a mean improvement of 7.8 points (P = .002) in the pembrolizumab patients compared with the chemotherapy patients, a difference Dr. Brahmer called “clinically meaningful” as well as statistically significant.
A second analysis of patient-reported outcomes used a second EORTC instrument, the QLC-LC13, which combines assessment of cough, chest pain, and dyspnea. Treatment with pembrolizumab significantly reduced the time to deterioration as measured by this questionnaire by a relative 34%, (P = .029).
A third analysis looked at 15 individual function or symptom domains that make up the QLQ-C30. In general, these showed more improvements with pembrolizumab than with chemotherapy. One notable subcategory was fatigue, which showed significant improvement with pembrolizumab compared with a small worsening with chemotherapy.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This is a very nice analysis using a well-validated group of instruments to assess quality of life. The researchers also achieved a high level of compliance, with 79%-85% of patients completing the quality-of life questionnaire at 15 weeks, when the primary measure of health status occurred.
The mean difference of the weighted global health status score of 7.8 points between the pembrolizumab and chemotherapy patients was a little less than a minimally important difference, but in the context of a randomized, controlled trial this difference probably tells us that there is health status improvement in the pembrolizumab patients. In addition, the individual symptom and function domains showed that in general pembrolizumab performed better than chemotherapy.
Michael Boyer, MD , is professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from Pfizer, Roche, Eli Lilly, BMS, AstraZeneca, and Clovis. He made these comments as designated discussant for the report.
This is a very nice analysis using a well-validated group of instruments to assess quality of life. The researchers also achieved a high level of compliance, with 79%-85% of patients completing the quality-of life questionnaire at 15 weeks, when the primary measure of health status occurred.
The mean difference of the weighted global health status score of 7.8 points between the pembrolizumab and chemotherapy patients was a little less than a minimally important difference, but in the context of a randomized, controlled trial this difference probably tells us that there is health status improvement in the pembrolizumab patients. In addition, the individual symptom and function domains showed that in general pembrolizumab performed better than chemotherapy.
Michael Boyer, MD , is professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from Pfizer, Roche, Eli Lilly, BMS, AstraZeneca, and Clovis. He made these comments as designated discussant for the report.
This is a very nice analysis using a well-validated group of instruments to assess quality of life. The researchers also achieved a high level of compliance, with 79%-85% of patients completing the quality-of life questionnaire at 15 weeks, when the primary measure of health status occurred.
The mean difference of the weighted global health status score of 7.8 points between the pembrolizumab and chemotherapy patients was a little less than a minimally important difference, but in the context of a randomized, controlled trial this difference probably tells us that there is health status improvement in the pembrolizumab patients. In addition, the individual symptom and function domains showed that in general pembrolizumab performed better than chemotherapy.
Michael Boyer, MD , is professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from Pfizer, Roche, Eli Lilly, BMS, AstraZeneca, and Clovis. He made these comments as designated discussant for the report.
VIENNA – Patients with metastatic non–small-cell lung cancer with high levels of PD-L1 who received first-line pembrolizumab treatment had clinically meaningful improvement in their quality of life, compared with patients randomized to chemotherapy, in a prespecified secondary analysis of data from the drug’s pivotal trial.
This boost in quality of life as well as other measures of health status add to the pivotal trial’s primary finding of significantly increased progression-free survival compared with chemotherapy, as well as previously-reported secondary findings of superior overall survival, objective response rate, and safety with pembrolizumab compared with chemotherapy (N Engl J Med. 2016 Nov 10;375[19]:1823-33), Julie R. Brahmer, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
The primary endpoint of the Study of Pembrolizumab Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non–Small Cell Lung Cancer (KEYNOTE-024) showed an average 4.3-month increase in progression-free survival with pembrolizumab immunotherapy, compared with a standard chemotherapy regimen.
Improved quality of life on top of improved efficacy and safety is an important added benefit from pembrolizumab that should further spur its widespread adoption as first-line treatment for approved patients, Dr. Brahmer said in a video interview.
“When you talk about improving efficacy by months, patients and physicians want to also see improved quality of life,” said Dr. Brahmer, director of thoracic oncology at the Johns Hopkins Kimmel Cancer Center in Baltimore. “If symptoms are not improved or there are a ton of side effects with the treatment then use might be low.”
Based on its performance in KEYNOTE-024, pembrolizumab (Keytruda) received Food and Drug Administration approval on Oct. 24, 2016, as first-line treatment for patients with metastatic non–small-cell lung cancer that has a tumor proportion score of at least 50% for programmed death ligand 1 (PD-L1). Pembrolizumab is a monoclonal antibody that binds and blocks PD-1, the immune-cell receptor that tumor-cell PD-L1 binds to make immune cells less active. Other new immune checkpoint inhibitor drugs that act by blocking PD-1 or PD-L1 have shown similar quality of life benefits, she noted.
Routine availability of pembrolizumab as initial treatment for patients who have tumors with this level of PD-L1 expression (and also have no EGFR or ALK genomic aberrations) is shifting practice, Dr. Brahmer said.
“It’s catching on. The limitation right now is making sure patients get tested” for their PD-L1 tumor proportion score at the time they are first diagnosed. “Medical oncologists need to educate pathologists that we need this testing automatically, upfront. It’s not there yet,” she said.
Patients also are enthused. “There is a lot of chemo-exhaustion among patients. They are looking for something different, and something that uses their immune system makes sense.” But only about one quarter of patients have tumors with this level of PD-L1 expression; the others must start chemotherapy first before trying immunotherapy, unless they have an EGFR mutation. Out-of-pocket cost for pembrolizumab is also a major issues for many patients, she said.
KEYNOTE-024 randomized 305 patients at 102 international sites and followed patients for a median of 11 months. Dr. Brahmer and her associates made two primary analyses of patient-reported outcomes. One was measurement of global health status at 15 weeks after the start of treatment using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire designed to assess quality of life. Weighted averaging of the EORTC QCQ-C30 scores showed a mean improvement of 7.8 points (P = .002) in the pembrolizumab patients compared with the chemotherapy patients, a difference Dr. Brahmer called “clinically meaningful” as well as statistically significant.
A second analysis of patient-reported outcomes used a second EORTC instrument, the QLC-LC13, which combines assessment of cough, chest pain, and dyspnea. Treatment with pembrolizumab significantly reduced the time to deterioration as measured by this questionnaire by a relative 34%, (P = .029).
A third analysis looked at 15 individual function or symptom domains that make up the QLQ-C30. In general, these showed more improvements with pembrolizumab than with chemotherapy. One notable subcategory was fatigue, which showed significant improvement with pembrolizumab compared with a small worsening with chemotherapy.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Patients with metastatic non–small-cell lung cancer with high levels of PD-L1 who received first-line pembrolizumab treatment had clinically meaningful improvement in their quality of life, compared with patients randomized to chemotherapy, in a prespecified secondary analysis of data from the drug’s pivotal trial.
This boost in quality of life as well as other measures of health status add to the pivotal trial’s primary finding of significantly increased progression-free survival compared with chemotherapy, as well as previously-reported secondary findings of superior overall survival, objective response rate, and safety with pembrolizumab compared with chemotherapy (N Engl J Med. 2016 Nov 10;375[19]:1823-33), Julie R. Brahmer, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
The primary endpoint of the Study of Pembrolizumab Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non–Small Cell Lung Cancer (KEYNOTE-024) showed an average 4.3-month increase in progression-free survival with pembrolizumab immunotherapy, compared with a standard chemotherapy regimen.
Improved quality of life on top of improved efficacy and safety is an important added benefit from pembrolizumab that should further spur its widespread adoption as first-line treatment for approved patients, Dr. Brahmer said in a video interview.
“When you talk about improving efficacy by months, patients and physicians want to also see improved quality of life,” said Dr. Brahmer, director of thoracic oncology at the Johns Hopkins Kimmel Cancer Center in Baltimore. “If symptoms are not improved or there are a ton of side effects with the treatment then use might be low.”
Based on its performance in KEYNOTE-024, pembrolizumab (Keytruda) received Food and Drug Administration approval on Oct. 24, 2016, as first-line treatment for patients with metastatic non–small-cell lung cancer that has a tumor proportion score of at least 50% for programmed death ligand 1 (PD-L1). Pembrolizumab is a monoclonal antibody that binds and blocks PD-1, the immune-cell receptor that tumor-cell PD-L1 binds to make immune cells less active. Other new immune checkpoint inhibitor drugs that act by blocking PD-1 or PD-L1 have shown similar quality of life benefits, she noted.
Routine availability of pembrolizumab as initial treatment for patients who have tumors with this level of PD-L1 expression (and also have no EGFR or ALK genomic aberrations) is shifting practice, Dr. Brahmer said.
“It’s catching on. The limitation right now is making sure patients get tested” for their PD-L1 tumor proportion score at the time they are first diagnosed. “Medical oncologists need to educate pathologists that we need this testing automatically, upfront. It’s not there yet,” she said.
Patients also are enthused. “There is a lot of chemo-exhaustion among patients. They are looking for something different, and something that uses their immune system makes sense.” But only about one quarter of patients have tumors with this level of PD-L1 expression; the others must start chemotherapy first before trying immunotherapy, unless they have an EGFR mutation. Out-of-pocket cost for pembrolizumab is also a major issues for many patients, she said.
KEYNOTE-024 randomized 305 patients at 102 international sites and followed patients for a median of 11 months. Dr. Brahmer and her associates made two primary analyses of patient-reported outcomes. One was measurement of global health status at 15 weeks after the start of treatment using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire designed to assess quality of life. Weighted averaging of the EORTC QCQ-C30 scores showed a mean improvement of 7.8 points (P = .002) in the pembrolizumab patients compared with the chemotherapy patients, a difference Dr. Brahmer called “clinically meaningful” as well as statistically significant.
A second analysis of patient-reported outcomes used a second EORTC instrument, the QLC-LC13, which combines assessment of cough, chest pain, and dyspnea. Treatment with pembrolizumab significantly reduced the time to deterioration as measured by this questionnaire by a relative 34%, (P = .029).
A third analysis looked at 15 individual function or symptom domains that make up the QLQ-C30. In general, these showed more improvements with pembrolizumab than with chemotherapy. One notable subcategory was fatigue, which showed significant improvement with pembrolizumab compared with a small worsening with chemotherapy.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCLC 2016
Key clinical point:
Major finding: The weighted average change from baseline in QLQ-C30 was 7.8 points higher in pembrolizumab patients compared with chemotherapy patients.
Data source: KEYNOTE-024, a multicenter, international randomized trial comprising 305 patients.
Disclosures: Merck, which markets pembrolizumab (Keytruda), sponsored KEYNOTE-024. Dr. Brahmer has served on an advisory board for Merck.
Toxicity high for SBRT in centrally-located lung tumors
VIENNA – Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.
The majority of patients experienced some type of adverse effect, with 28% experiencing serious (grade 3-5) adverse effects.
“Our major concern now is that we had six cases of grade 5 bleedings,” Karen Lindberg, MD, said at the World Conference on Lung Cancer. “Tumor location seems to be a risk factor for bleeding,” she added, with five of the six cases seen in patients who had tumors close to a main bronchus (group A). The other case was in patient who had tumors close to a lobular bronchus (group B).
“The classical definition of a centrally-located lung tumor is a tumor residing within or touching an imaginary zone 2 cm around the proximal bronchial tree,” explained Dr. Lindberg of Karolinska University Hospital and the Karolinska Institutet in Stockholm, who presented the first results of the Nordic HILUS Trial.
“When we designed this study we wanted to look at very centrally located tumors, so we tightened up this definition to look at tumors that occurred within 1 cm around the proximal bronchial tree,” she said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
During the trial, SBRT was to be delivered at a dose of 7 Gray (Gy) in 8 fractions at 65%-75% isodose lines to ultra-centrally-located tumors. Dose constraints were stipulated for tumors situated very close to the spinal cord, contralateral main bronchus, and trachea, with some dosing recommendations on reducing the dose delivered to tumors that were ipsilateral to the main bronchus, or very close to the esophagus or heart.
A total of 74 patients with centrally-located, locally progressive tumors, which were less than 5 cm in size and due to non–small-cell lung cancer (NSCLC) or metastatic lung disease from another solid tumor, were recruited. Patients had to have a good performance status and life expectancy of 3 months.
Patients with brain metastases or tumors that reached through the wall of a main bronchus were excluded as were those who were taking any concomitant systemic therapy.
The mean age of the recruited patients was 71 years; 58 (78%) had NSCLC, of which 20 (27%) had adenomas and 19 (26%) had squamous cell cancers. Of those with secondary lung tumors, eight (11%), had primary renal cell carcinoma and four (5%) had colorectal cancer.
After a follow-up of 18.6 months, 31 (42%) patients had died.
The most common adverse events reported were grade 1-2 dyspnea, cough, and fatigue. However, there was a high rate of grade 3 (dyspnea, fatigue, pain, pneumonitis, and heart rhythm disturbance), 4 (pain, lung infection, fever, heart rhythm disturbance, fistula, and pneumothorax) and 5 toxicities (pneumonitis and bleeding).
Bleeding often occurred without warning and had an acute onset and toll.
Seven patients (six in group A and one in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21 months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. The reintroduction of TKIs may also have played a role, Dr. Lindberg suggested.
SBRT for early stage NSCLC is very effective and “generates outstanding tumor control”, said Feng-Ming Kong, MD, of Indiana University, Indianapolis, who was invited to comment on the findings.
Most studies of SBRT have looked at peripherally-located tumors, however, so the study by the NORDIC Study Group provides valuable information on a more centrally-located approach. The big question of course is what caused the bleeding.
“What percentage of TKI patients had bleeding and how many of them had a TKI without bleeding?” Dr. Kong asked. Other questions around dosing remain: How much radiation was delivered to the great vessels such as the pulmonary artery, and how much of the dose hit critical structures? And, were tumors invading the pulmonary artery?
“SBRT may be applied for centrally-located tumors safely with other prescription regimens, she suggested, such as 10-11 Gy given in 5 fractions. That is assuming that “the dose limits of normal tissues are strictly controlled and the patients are carefully selected to exclude T4 diseases for adjacent organ invasion.”
The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.
VIENNA – Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.
The majority of patients experienced some type of adverse effect, with 28% experiencing serious (grade 3-5) adverse effects.
“Our major concern now is that we had six cases of grade 5 bleedings,” Karen Lindberg, MD, said at the World Conference on Lung Cancer. “Tumor location seems to be a risk factor for bleeding,” she added, with five of the six cases seen in patients who had tumors close to a main bronchus (group A). The other case was in patient who had tumors close to a lobular bronchus (group B).
“The classical definition of a centrally-located lung tumor is a tumor residing within or touching an imaginary zone 2 cm around the proximal bronchial tree,” explained Dr. Lindberg of Karolinska University Hospital and the Karolinska Institutet in Stockholm, who presented the first results of the Nordic HILUS Trial.
“When we designed this study we wanted to look at very centrally located tumors, so we tightened up this definition to look at tumors that occurred within 1 cm around the proximal bronchial tree,” she said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
During the trial, SBRT was to be delivered at a dose of 7 Gray (Gy) in 8 fractions at 65%-75% isodose lines to ultra-centrally-located tumors. Dose constraints were stipulated for tumors situated very close to the spinal cord, contralateral main bronchus, and trachea, with some dosing recommendations on reducing the dose delivered to tumors that were ipsilateral to the main bronchus, or very close to the esophagus or heart.
A total of 74 patients with centrally-located, locally progressive tumors, which were less than 5 cm in size and due to non–small-cell lung cancer (NSCLC) or metastatic lung disease from another solid tumor, were recruited. Patients had to have a good performance status and life expectancy of 3 months.
Patients with brain metastases or tumors that reached through the wall of a main bronchus were excluded as were those who were taking any concomitant systemic therapy.
The mean age of the recruited patients was 71 years; 58 (78%) had NSCLC, of which 20 (27%) had adenomas and 19 (26%) had squamous cell cancers. Of those with secondary lung tumors, eight (11%), had primary renal cell carcinoma and four (5%) had colorectal cancer.
After a follow-up of 18.6 months, 31 (42%) patients had died.
The most common adverse events reported were grade 1-2 dyspnea, cough, and fatigue. However, there was a high rate of grade 3 (dyspnea, fatigue, pain, pneumonitis, and heart rhythm disturbance), 4 (pain, lung infection, fever, heart rhythm disturbance, fistula, and pneumothorax) and 5 toxicities (pneumonitis and bleeding).
Bleeding often occurred without warning and had an acute onset and toll.
Seven patients (six in group A and one in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21 months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. The reintroduction of TKIs may also have played a role, Dr. Lindberg suggested.
SBRT for early stage NSCLC is very effective and “generates outstanding tumor control”, said Feng-Ming Kong, MD, of Indiana University, Indianapolis, who was invited to comment on the findings.
Most studies of SBRT have looked at peripherally-located tumors, however, so the study by the NORDIC Study Group provides valuable information on a more centrally-located approach. The big question of course is what caused the bleeding.
“What percentage of TKI patients had bleeding and how many of them had a TKI without bleeding?” Dr. Kong asked. Other questions around dosing remain: How much radiation was delivered to the great vessels such as the pulmonary artery, and how much of the dose hit critical structures? And, were tumors invading the pulmonary artery?
“SBRT may be applied for centrally-located tumors safely with other prescription regimens, she suggested, such as 10-11 Gy given in 5 fractions. That is assuming that “the dose limits of normal tissues are strictly controlled and the patients are carefully selected to exclude T4 diseases for adjacent organ invasion.”
The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.
VIENNA – Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.
The majority of patients experienced some type of adverse effect, with 28% experiencing serious (grade 3-5) adverse effects.
“Our major concern now is that we had six cases of grade 5 bleedings,” Karen Lindberg, MD, said at the World Conference on Lung Cancer. “Tumor location seems to be a risk factor for bleeding,” she added, with five of the six cases seen in patients who had tumors close to a main bronchus (group A). The other case was in patient who had tumors close to a lobular bronchus (group B).
“The classical definition of a centrally-located lung tumor is a tumor residing within or touching an imaginary zone 2 cm around the proximal bronchial tree,” explained Dr. Lindberg of Karolinska University Hospital and the Karolinska Institutet in Stockholm, who presented the first results of the Nordic HILUS Trial.
“When we designed this study we wanted to look at very centrally located tumors, so we tightened up this definition to look at tumors that occurred within 1 cm around the proximal bronchial tree,” she said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
During the trial, SBRT was to be delivered at a dose of 7 Gray (Gy) in 8 fractions at 65%-75% isodose lines to ultra-centrally-located tumors. Dose constraints were stipulated for tumors situated very close to the spinal cord, contralateral main bronchus, and trachea, with some dosing recommendations on reducing the dose delivered to tumors that were ipsilateral to the main bronchus, or very close to the esophagus or heart.
A total of 74 patients with centrally-located, locally progressive tumors, which were less than 5 cm in size and due to non–small-cell lung cancer (NSCLC) or metastatic lung disease from another solid tumor, were recruited. Patients had to have a good performance status and life expectancy of 3 months.
Patients with brain metastases or tumors that reached through the wall of a main bronchus were excluded as were those who were taking any concomitant systemic therapy.
The mean age of the recruited patients was 71 years; 58 (78%) had NSCLC, of which 20 (27%) had adenomas and 19 (26%) had squamous cell cancers. Of those with secondary lung tumors, eight (11%), had primary renal cell carcinoma and four (5%) had colorectal cancer.
After a follow-up of 18.6 months, 31 (42%) patients had died.
The most common adverse events reported were grade 1-2 dyspnea, cough, and fatigue. However, there was a high rate of grade 3 (dyspnea, fatigue, pain, pneumonitis, and heart rhythm disturbance), 4 (pain, lung infection, fever, heart rhythm disturbance, fistula, and pneumothorax) and 5 toxicities (pneumonitis and bleeding).
Bleeding often occurred without warning and had an acute onset and toll.
Seven patients (six in group A and one in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21 months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. The reintroduction of TKIs may also have played a role, Dr. Lindberg suggested.
SBRT for early stage NSCLC is very effective and “generates outstanding tumor control”, said Feng-Ming Kong, MD, of Indiana University, Indianapolis, who was invited to comment on the findings.
Most studies of SBRT have looked at peripherally-located tumors, however, so the study by the NORDIC Study Group provides valuable information on a more centrally-located approach. The big question of course is what caused the bleeding.
“What percentage of TKI patients had bleeding and how many of them had a TKI without bleeding?” Dr. Kong asked. Other questions around dosing remain: How much radiation was delivered to the great vessels such as the pulmonary artery, and how much of the dose hit critical structures? And, were tumors invading the pulmonary artery?
“SBRT may be applied for centrally-located tumors safely with other prescription regimens, she suggested, such as 10-11 Gy given in 5 fractions. That is assuming that “the dose limits of normal tissues are strictly controlled and the patients are carefully selected to exclude T4 diseases for adjacent organ invasion.”
The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.
AT WCLC 2016
Key clinical point: Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.
Major finding: There was a high rate of grade 3, 4, and 5 toxicities, including six cases of grade 5 bleeding.
Data source: The phase II non-randomized HILUS trial of 74 patients with centrally-located lung tumors treated with SBRT.
Disclosures: The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.
c-Myc could be key to alisertib potential in small-cell lung cancer
VIENNA – The investigational agent alisertib plus paclitaxel improved progression-free survival (PFS), compared with paclitaxel plus placebo, in a randomized, double-blind, phase II study of patients with relapsed or refractory small-cell lung cancer (SCLC).
The median PFS was 3.32 months with alisertib/paclitaxel and 2.17 months with paclitaxel/placebo, giving an overall 30% improvement with the combination (hazard ratio, 0.71; 95% confidence interval, 0.509-0.985; P = .038).
“c-Myc protein expression showed a strong association with improved PFS, despite the small number of evaluable patients,” study investigator Taofeek Owonikoko, MD, of Emory University, Atlanta, said at the World Conference on Lung Cancer.
Amplification and overexpression of c-Myc is a strong oncogenic driver in many cancers, he explained. Around 18%-31% of SCLCs overexpress the protein, and it is often found in patients with chemorefractory disease, he said.
In the study, longer PFS was achieved in patients treated with alisertib/paclitaxel than in those given placebo/paclitaxel if they were c-Myc positive (4.64 vs. 2.27 months; HR, 0.29). Conversely, patients who were c-Myc negative had a shorter PFS with the combination (3.32 vs. 5.16 months; HR, 11.8).
“A prospective study is needed to further validate the predictive value of c-Myc in the clinic,” Dr. Owonikoko said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
Alisertib is an aurora A kinase inhibitor that has already been shown to have antitumor activity in patients with solid tumors, including those with SCLC (Lancet Oncol. 2015;16[4]:395-405).
The current phase II study was designed to evaluate the efficacy and safety of alisertib in combination with paclitaxel, compared with placebo plus paclitaxel, in a larger population of patients with SCLC who had relapsed within 6 months or did not respond to standard first-line, platinum-based chemotherapy.
Treatment was given in 28-day cycles, with patients randomized to the combination receiving alisertib at an oral, 40-mg, twice-daily dose on days 1-3, 8-10, and 15-17 and paclitaxel administered intravenously at a dose of 60 mg/m2 IV on days 1, 8, 15. Patients randomized to the control arm received a matched placebo plus paclitaxel given on the same days but at a dose of 80 mg/m2.
Overall, 178 patients were randomized, with a mean age of 62 years, and just over half (57%) were men.
Numerically higher objective response rates (22% vs. 18%), disease control rates (77 vs. 67%), and overall survival (6.87 vs. 5.58 months) also were seen with the combination over paclitaxel alone, although they did not achieve statistical significance.
Additional toxicities were observed with the combination treatment versus paclitaxel. Many of these were to be expected, Dr. Owonikoko said. Almost all (99% vs. 96%) of patients reported some type of adverse event, of which 75% and 51% were grade 3 or higher, respectively. Common any-grade adverse effects were diarrhea (59% vs. 20%), neutropenia (49% vs. 8%), anemia (44% vs. 20%), and fatigue (44% vs. 33%).
These toxicities, however, did not appear to affect patients’ quality of life, Dr. Owonikoko said, as comparable changes in quality-of-life scores using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument were observed. There was even an indication that patients taking alisertib/paclitaxel might have improved lung-related symptoms, such as shortness of breath and worsening cough.
The treatment of SCLC, particularly in the second-line setting, remains challenging, observed the invited discussant for the trial Jens Benn Sørensen, MD, of the Finsen Centre at Rigshospitalet, Copenhagen.
“There have been no major improvements in the last decade and there are no targeted agents approved for use,” Dr. Sørensen said. Although that is not for lack of trying, he qualified.
When first-line therapies fail, the guideline-recommended option is to put patients back on platinum-based chemotherapy if they were sensitive to such chemotherapy. If not, then topotecan is often an appropriate, reasonably tolerated option.
“The clinical relevance of second-line paclitaxel/alisertib in all comers is questionable,” he said. The PFS improvement of 1.2 months in this phase II study seems “mostly at the same level” when comparing trials of second-line, single-agent topotecan.
“However, the use of c-Myc as a predictor for efficacy seems very promising and should clearly be explored,” Dr. Sørensen noted.
He also suggested that it might be interesting to look into the combination of topotecan and alisertib versus topotecan alone in c-Myc-positive patients.
The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen did not have disclosures.
VIENNA – The investigational agent alisertib plus paclitaxel improved progression-free survival (PFS), compared with paclitaxel plus placebo, in a randomized, double-blind, phase II study of patients with relapsed or refractory small-cell lung cancer (SCLC).
The median PFS was 3.32 months with alisertib/paclitaxel and 2.17 months with paclitaxel/placebo, giving an overall 30% improvement with the combination (hazard ratio, 0.71; 95% confidence interval, 0.509-0.985; P = .038).
“c-Myc protein expression showed a strong association with improved PFS, despite the small number of evaluable patients,” study investigator Taofeek Owonikoko, MD, of Emory University, Atlanta, said at the World Conference on Lung Cancer.
Amplification and overexpression of c-Myc is a strong oncogenic driver in many cancers, he explained. Around 18%-31% of SCLCs overexpress the protein, and it is often found in patients with chemorefractory disease, he said.
In the study, longer PFS was achieved in patients treated with alisertib/paclitaxel than in those given placebo/paclitaxel if they were c-Myc positive (4.64 vs. 2.27 months; HR, 0.29). Conversely, patients who were c-Myc negative had a shorter PFS with the combination (3.32 vs. 5.16 months; HR, 11.8).
“A prospective study is needed to further validate the predictive value of c-Myc in the clinic,” Dr. Owonikoko said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
Alisertib is an aurora A kinase inhibitor that has already been shown to have antitumor activity in patients with solid tumors, including those with SCLC (Lancet Oncol. 2015;16[4]:395-405).
The current phase II study was designed to evaluate the efficacy and safety of alisertib in combination with paclitaxel, compared with placebo plus paclitaxel, in a larger population of patients with SCLC who had relapsed within 6 months or did not respond to standard first-line, platinum-based chemotherapy.
Treatment was given in 28-day cycles, with patients randomized to the combination receiving alisertib at an oral, 40-mg, twice-daily dose on days 1-3, 8-10, and 15-17 and paclitaxel administered intravenously at a dose of 60 mg/m2 IV on days 1, 8, 15. Patients randomized to the control arm received a matched placebo plus paclitaxel given on the same days but at a dose of 80 mg/m2.
Overall, 178 patients were randomized, with a mean age of 62 years, and just over half (57%) were men.
Numerically higher objective response rates (22% vs. 18%), disease control rates (77 vs. 67%), and overall survival (6.87 vs. 5.58 months) also were seen with the combination over paclitaxel alone, although they did not achieve statistical significance.
Additional toxicities were observed with the combination treatment versus paclitaxel. Many of these were to be expected, Dr. Owonikoko said. Almost all (99% vs. 96%) of patients reported some type of adverse event, of which 75% and 51% were grade 3 or higher, respectively. Common any-grade adverse effects were diarrhea (59% vs. 20%), neutropenia (49% vs. 8%), anemia (44% vs. 20%), and fatigue (44% vs. 33%).
These toxicities, however, did not appear to affect patients’ quality of life, Dr. Owonikoko said, as comparable changes in quality-of-life scores using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument were observed. There was even an indication that patients taking alisertib/paclitaxel might have improved lung-related symptoms, such as shortness of breath and worsening cough.
The treatment of SCLC, particularly in the second-line setting, remains challenging, observed the invited discussant for the trial Jens Benn Sørensen, MD, of the Finsen Centre at Rigshospitalet, Copenhagen.
“There have been no major improvements in the last decade and there are no targeted agents approved for use,” Dr. Sørensen said. Although that is not for lack of trying, he qualified.
When first-line therapies fail, the guideline-recommended option is to put patients back on platinum-based chemotherapy if they were sensitive to such chemotherapy. If not, then topotecan is often an appropriate, reasonably tolerated option.
“The clinical relevance of second-line paclitaxel/alisertib in all comers is questionable,” he said. The PFS improvement of 1.2 months in this phase II study seems “mostly at the same level” when comparing trials of second-line, single-agent topotecan.
“However, the use of c-Myc as a predictor for efficacy seems very promising and should clearly be explored,” Dr. Sørensen noted.
He also suggested that it might be interesting to look into the combination of topotecan and alisertib versus topotecan alone in c-Myc-positive patients.
The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen did not have disclosures.
VIENNA – The investigational agent alisertib plus paclitaxel improved progression-free survival (PFS), compared with paclitaxel plus placebo, in a randomized, double-blind, phase II study of patients with relapsed or refractory small-cell lung cancer (SCLC).
The median PFS was 3.32 months with alisertib/paclitaxel and 2.17 months with paclitaxel/placebo, giving an overall 30% improvement with the combination (hazard ratio, 0.71; 95% confidence interval, 0.509-0.985; P = .038).
“c-Myc protein expression showed a strong association with improved PFS, despite the small number of evaluable patients,” study investigator Taofeek Owonikoko, MD, of Emory University, Atlanta, said at the World Conference on Lung Cancer.
Amplification and overexpression of c-Myc is a strong oncogenic driver in many cancers, he explained. Around 18%-31% of SCLCs overexpress the protein, and it is often found in patients with chemorefractory disease, he said.
In the study, longer PFS was achieved in patients treated with alisertib/paclitaxel than in those given placebo/paclitaxel if they were c-Myc positive (4.64 vs. 2.27 months; HR, 0.29). Conversely, patients who were c-Myc negative had a shorter PFS with the combination (3.32 vs. 5.16 months; HR, 11.8).
“A prospective study is needed to further validate the predictive value of c-Myc in the clinic,” Dr. Owonikoko said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
Alisertib is an aurora A kinase inhibitor that has already been shown to have antitumor activity in patients with solid tumors, including those with SCLC (Lancet Oncol. 2015;16[4]:395-405).
The current phase II study was designed to evaluate the efficacy and safety of alisertib in combination with paclitaxel, compared with placebo plus paclitaxel, in a larger population of patients with SCLC who had relapsed within 6 months or did not respond to standard first-line, platinum-based chemotherapy.
Treatment was given in 28-day cycles, with patients randomized to the combination receiving alisertib at an oral, 40-mg, twice-daily dose on days 1-3, 8-10, and 15-17 and paclitaxel administered intravenously at a dose of 60 mg/m2 IV on days 1, 8, 15. Patients randomized to the control arm received a matched placebo plus paclitaxel given on the same days but at a dose of 80 mg/m2.
Overall, 178 patients were randomized, with a mean age of 62 years, and just over half (57%) were men.
Numerically higher objective response rates (22% vs. 18%), disease control rates (77 vs. 67%), and overall survival (6.87 vs. 5.58 months) also were seen with the combination over paclitaxel alone, although they did not achieve statistical significance.
Additional toxicities were observed with the combination treatment versus paclitaxel. Many of these were to be expected, Dr. Owonikoko said. Almost all (99% vs. 96%) of patients reported some type of adverse event, of which 75% and 51% were grade 3 or higher, respectively. Common any-grade adverse effects were diarrhea (59% vs. 20%), neutropenia (49% vs. 8%), anemia (44% vs. 20%), and fatigue (44% vs. 33%).
These toxicities, however, did not appear to affect patients’ quality of life, Dr. Owonikoko said, as comparable changes in quality-of-life scores using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument were observed. There was even an indication that patients taking alisertib/paclitaxel might have improved lung-related symptoms, such as shortness of breath and worsening cough.
The treatment of SCLC, particularly in the second-line setting, remains challenging, observed the invited discussant for the trial Jens Benn Sørensen, MD, of the Finsen Centre at Rigshospitalet, Copenhagen.
“There have been no major improvements in the last decade and there are no targeted agents approved for use,” Dr. Sørensen said. Although that is not for lack of trying, he qualified.
When first-line therapies fail, the guideline-recommended option is to put patients back on platinum-based chemotherapy if they were sensitive to such chemotherapy. If not, then topotecan is often an appropriate, reasonably tolerated option.
“The clinical relevance of second-line paclitaxel/alisertib in all comers is questionable,” he said. The PFS improvement of 1.2 months in this phase II study seems “mostly at the same level” when comparing trials of second-line, single-agent topotecan.
“However, the use of c-Myc as a predictor for efficacy seems very promising and should clearly be explored,” Dr. Sørensen noted.
He also suggested that it might be interesting to look into the combination of topotecan and alisertib versus topotecan alone in c-Myc-positive patients.
The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen did not have disclosures.
AT WCLC 2016
Key clinical point: Alisertib/paclitaxel is an investigational combination that was tested for the treatment of relapsed or refractory small-cell lung cancer (SCLC).
Major finding: Improved progression-free survival was seen with the combination versus paclitaxel alone (3.2 vs. 2.17 months, P less than .038).
Data source: Randomized, double-blind, multicenter, phase II study of alisertib/paclitaxel versus placebo/paclitaxel in 178 patients with relapsed or refractory SCLC.
Disclosures: The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen had no conflicts of interest to disclose.
Durvalumab could offer option for difficult-to-treat NSCLC
VIENNA – In a heavily pretreated population of patients with non–small-cell lung cancer (NSCLC), the investigational checkpoint inhibitor durvalumab was associated with good objective response rates (ORR) and ‘impressive’ overall survival (OS) in a phase II study, Marina Garassino, MD, reported at the World Conference on Lung Cancer.
The primary endpoint of ORR in the open-label, single-arm ATLANTIC trial was achieved by 7% of patients with low (less than 25% of tumor cells) expression of the programmed death ligand 1 (PD-L1) that durvalumab targets (n = 93), by 16.4% of patients with PD-L1 expression of 25% or higher (n = 146), and by 30.9% in patients with PD-L1 expression of 90% or more (n = 68).
Yet the results of ATLANTIC show not only that durvalumab is active, but also that it can produce long-lasting responses in patients who have been treated with a mean of three prior regimens, she reported.
The median duration of response to date was not reached in patients with PD-L1 expression of 25% or less, was 12.3 months in patients with greater than 25% PD-L1 expression, and had again not yet been reached in those with greater than 90% PD-L1 expression. At the time the data were pulled for analysis, June 2016, 18 of 21 patients in the latter group were progression free.
The disease control rate at 6 months was 20.4%, 28.8%, 38.2% for patients with PD-L1 expression of less than 25%, 25%-90%, and greater than 90%, respectively.
“One-year overall survival was about 48% in patients with PD-L1 greater than 25% and about 51% in those with PD-L1 greater than 90%,” Dr. Garassino said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
The respective median OS times for patients with 25% and greater and less than 25% PD-L1 expression were 10.9 (95% CI 8.6-13.6) and 9.3 (95% CI 5.9-10.8) months, and not yet reached for patients with 90% or greater PD-L1 expression.
“Most adverse events were low grade and immune mediated adverse events were easily manageable,” Dr. Garassino said. Overall, 10.2% of patients had grade 3 or 4 treatment-related adverse events and 2.7% had treatment-related adverse events that led to discontinuation.
Any immune-mediated adverse event occurred in 12.3% of patients, of which 6.3% were due to an underactive and 2.4% to a hyperactive thyroid.
“Results are consistent with other anti-PD-1/PD-L1 compounds in metastatic, relapsed NSCLC and we are awaiting the final results of phase III trials to clarify the role of durvalumab [treatment] alone or in combination in NSCLC,” Dr. Garassino said.
Overall, 1,990 patients were screened for inclusion in the ATLANTIC study, which recruited 444 patients with stage IIIB-IV NSCLC who had received at least two prior systemic treatments, one of which had to be platinum based and had a recent (within 3 months) tumor biopsy and archived tissue available for PD-L1 assessment. Dr. Garassino reported results for two of the three cohorts.
Durvalumab was given at an intravenous dose of 10 mg/kg every 2 weeks for up to 1 year. The mean number of prior regimens was 3.2 for patients with less than 25% and greater than or equal to 25% PD-L1 expression combined and 2.6 for those with greater than 90% PD-L1 expression.
“This drug clearly does have activity and we can see that in the response rates, which range from 7% all the way up to 31%,” said Michael Boyer, MBBS, chief clinical officer of Chris O’Brien Lifehouse in Melbourne, who was the invited discussant for the trial. “The higher the PD-L1 expression, the higher the response rate,” he observed.
“There was quite impressive survival, if you bear in mind that this is a third-line, or more than third-line cohort of patients, with a median overall survival in the strongest PD-L1 expressing patients that is clearly going to exceed 1 year” he added.
The big question for the future is what will be the relevance of having an immunotherapy that works well in such a heavily pretreated population when these drugs are more likely to be used second- or even first-line, especially in those who have high PD-L1 expression where the drug seems to be at its most effective, Dr. Boyer said.
AstraZeneca funded the study. Dr. Garassino disclosed relationships with AstraZeneca, Bristol Myers Squibb, Roche, Merck, Sharp & Dohme, Boehringer Ingelheim, and Eli Lilly. Dr. Boyer disclosed that he had received research funding, honoraria, or both that were paid to his institution from Pfizer, Roche, Eli Lilly, Merck, Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, and Clovis.
VIENNA – In a heavily pretreated population of patients with non–small-cell lung cancer (NSCLC), the investigational checkpoint inhibitor durvalumab was associated with good objective response rates (ORR) and ‘impressive’ overall survival (OS) in a phase II study, Marina Garassino, MD, reported at the World Conference on Lung Cancer.
The primary endpoint of ORR in the open-label, single-arm ATLANTIC trial was achieved by 7% of patients with low (less than 25% of tumor cells) expression of the programmed death ligand 1 (PD-L1) that durvalumab targets (n = 93), by 16.4% of patients with PD-L1 expression of 25% or higher (n = 146), and by 30.9% in patients with PD-L1 expression of 90% or more (n = 68).
Yet the results of ATLANTIC show not only that durvalumab is active, but also that it can produce long-lasting responses in patients who have been treated with a mean of three prior regimens, she reported.
The median duration of response to date was not reached in patients with PD-L1 expression of 25% or less, was 12.3 months in patients with greater than 25% PD-L1 expression, and had again not yet been reached in those with greater than 90% PD-L1 expression. At the time the data were pulled for analysis, June 2016, 18 of 21 patients in the latter group were progression free.
The disease control rate at 6 months was 20.4%, 28.8%, 38.2% for patients with PD-L1 expression of less than 25%, 25%-90%, and greater than 90%, respectively.
“One-year overall survival was about 48% in patients with PD-L1 greater than 25% and about 51% in those with PD-L1 greater than 90%,” Dr. Garassino said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
The respective median OS times for patients with 25% and greater and less than 25% PD-L1 expression were 10.9 (95% CI 8.6-13.6) and 9.3 (95% CI 5.9-10.8) months, and not yet reached for patients with 90% or greater PD-L1 expression.
“Most adverse events were low grade and immune mediated adverse events were easily manageable,” Dr. Garassino said. Overall, 10.2% of patients had grade 3 or 4 treatment-related adverse events and 2.7% had treatment-related adverse events that led to discontinuation.
Any immune-mediated adverse event occurred in 12.3% of patients, of which 6.3% were due to an underactive and 2.4% to a hyperactive thyroid.
“Results are consistent with other anti-PD-1/PD-L1 compounds in metastatic, relapsed NSCLC and we are awaiting the final results of phase III trials to clarify the role of durvalumab [treatment] alone or in combination in NSCLC,” Dr. Garassino said.
Overall, 1,990 patients were screened for inclusion in the ATLANTIC study, which recruited 444 patients with stage IIIB-IV NSCLC who had received at least two prior systemic treatments, one of which had to be platinum based and had a recent (within 3 months) tumor biopsy and archived tissue available for PD-L1 assessment. Dr. Garassino reported results for two of the three cohorts.
Durvalumab was given at an intravenous dose of 10 mg/kg every 2 weeks for up to 1 year. The mean number of prior regimens was 3.2 for patients with less than 25% and greater than or equal to 25% PD-L1 expression combined and 2.6 for those with greater than 90% PD-L1 expression.
“This drug clearly does have activity and we can see that in the response rates, which range from 7% all the way up to 31%,” said Michael Boyer, MBBS, chief clinical officer of Chris O’Brien Lifehouse in Melbourne, who was the invited discussant for the trial. “The higher the PD-L1 expression, the higher the response rate,” he observed.
“There was quite impressive survival, if you bear in mind that this is a third-line, or more than third-line cohort of patients, with a median overall survival in the strongest PD-L1 expressing patients that is clearly going to exceed 1 year” he added.
The big question for the future is what will be the relevance of having an immunotherapy that works well in such a heavily pretreated population when these drugs are more likely to be used second- or even first-line, especially in those who have high PD-L1 expression where the drug seems to be at its most effective, Dr. Boyer said.
AstraZeneca funded the study. Dr. Garassino disclosed relationships with AstraZeneca, Bristol Myers Squibb, Roche, Merck, Sharp & Dohme, Boehringer Ingelheim, and Eli Lilly. Dr. Boyer disclosed that he had received research funding, honoraria, or both that were paid to his institution from Pfizer, Roche, Eli Lilly, Merck, Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, and Clovis.
VIENNA – In a heavily pretreated population of patients with non–small-cell lung cancer (NSCLC), the investigational checkpoint inhibitor durvalumab was associated with good objective response rates (ORR) and ‘impressive’ overall survival (OS) in a phase II study, Marina Garassino, MD, reported at the World Conference on Lung Cancer.
The primary endpoint of ORR in the open-label, single-arm ATLANTIC trial was achieved by 7% of patients with low (less than 25% of tumor cells) expression of the programmed death ligand 1 (PD-L1) that durvalumab targets (n = 93), by 16.4% of patients with PD-L1 expression of 25% or higher (n = 146), and by 30.9% in patients with PD-L1 expression of 90% or more (n = 68).
Yet the results of ATLANTIC show not only that durvalumab is active, but also that it can produce long-lasting responses in patients who have been treated with a mean of three prior regimens, she reported.
The median duration of response to date was not reached in patients with PD-L1 expression of 25% or less, was 12.3 months in patients with greater than 25% PD-L1 expression, and had again not yet been reached in those with greater than 90% PD-L1 expression. At the time the data were pulled for analysis, June 2016, 18 of 21 patients in the latter group were progression free.
The disease control rate at 6 months was 20.4%, 28.8%, 38.2% for patients with PD-L1 expression of less than 25%, 25%-90%, and greater than 90%, respectively.
“One-year overall survival was about 48% in patients with PD-L1 greater than 25% and about 51% in those with PD-L1 greater than 90%,” Dr. Garassino said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
The respective median OS times for patients with 25% and greater and less than 25% PD-L1 expression were 10.9 (95% CI 8.6-13.6) and 9.3 (95% CI 5.9-10.8) months, and not yet reached for patients with 90% or greater PD-L1 expression.
“Most adverse events were low grade and immune mediated adverse events were easily manageable,” Dr. Garassino said. Overall, 10.2% of patients had grade 3 or 4 treatment-related adverse events and 2.7% had treatment-related adverse events that led to discontinuation.
Any immune-mediated adverse event occurred in 12.3% of patients, of which 6.3% were due to an underactive and 2.4% to a hyperactive thyroid.
“Results are consistent with other anti-PD-1/PD-L1 compounds in metastatic, relapsed NSCLC and we are awaiting the final results of phase III trials to clarify the role of durvalumab [treatment] alone or in combination in NSCLC,” Dr. Garassino said.
Overall, 1,990 patients were screened for inclusion in the ATLANTIC study, which recruited 444 patients with stage IIIB-IV NSCLC who had received at least two prior systemic treatments, one of which had to be platinum based and had a recent (within 3 months) tumor biopsy and archived tissue available for PD-L1 assessment. Dr. Garassino reported results for two of the three cohorts.
Durvalumab was given at an intravenous dose of 10 mg/kg every 2 weeks for up to 1 year. The mean number of prior regimens was 3.2 for patients with less than 25% and greater than or equal to 25% PD-L1 expression combined and 2.6 for those with greater than 90% PD-L1 expression.
“This drug clearly does have activity and we can see that in the response rates, which range from 7% all the way up to 31%,” said Michael Boyer, MBBS, chief clinical officer of Chris O’Brien Lifehouse in Melbourne, who was the invited discussant for the trial. “The higher the PD-L1 expression, the higher the response rate,” he observed.
“There was quite impressive survival, if you bear in mind that this is a third-line, or more than third-line cohort of patients, with a median overall survival in the strongest PD-L1 expressing patients that is clearly going to exceed 1 year” he added.
The big question for the future is what will be the relevance of having an immunotherapy that works well in such a heavily pretreated population when these drugs are more likely to be used second- or even first-line, especially in those who have high PD-L1 expression where the drug seems to be at its most effective, Dr. Boyer said.
AstraZeneca funded the study. Dr. Garassino disclosed relationships with AstraZeneca, Bristol Myers Squibb, Roche, Merck, Sharp & Dohme, Boehringer Ingelheim, and Eli Lilly. Dr. Boyer disclosed that he had received research funding, honoraria, or both that were paid to his institution from Pfizer, Roche, Eli Lilly, Merck, Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, and Clovis.
Key clinical point: Durvalumab had substantial antitumor activity and produced long-lasting responses in patients with previously treated advanced non–small-cell lung cancer (NSCLC).
Major finding: Objective response rates of 16.4% and 30.1% were achieved in patients with the highest PD-L1 expression profiles.
Data source: Phase II, open-label, single-arm ATLANTIC trial of 444 patients with relapsed, locally advanced or metastatic NSCLC treated with two or more prior systemic regimens.
Disclosures: AstraZeneca funded the study. Dr. Garassino disclosed relationships with AstraZeneca, Bristol Myers Squibb, Roche, Merck, Sharp & Dohme, Boehringer Ingelheim, and Eli Lilly. Dr. Boyer disclosed that he had received research funding, honoraria, or both that were paid to his institution from Pfizer, Roche, Eli Lilly, Merck, Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, and Clovis.
KRAS-targeted T-cell therapy derails metastatic cancer
Adoptive transfer of cytotoxic T cells targeting a specific KRAS mutation (KRAS G12D) expressed by a metastatic colorectal cancer induced the regression of all seven lung metastases in a single patient, investigators report in the New England Journal of Medicine.
Mutations of the KRAS oncogene are frequent and drive the formation and progression of many human cancers. “The high incidence of KRAS G12D expression in [colorectal, pancreatic, and multiple other] cancers means that in the United States alone, thousands of patients per year would be potentially eligible for T-cell–based immunotherapy targeting KRAS G12D,” said Eric Tran, PhD, and his associates in the surgery branch, National Cancer Institute, Bethesda, Md.
They described the case of a 50-year-old woman participating in an ongoing phase II clinical trial assessing adoptive transfer of tumor-infiltrating lymphocytes targeting personalized cancer neoepitopes (individualized T-cell therapy). This patient was the only participant to date in whom the treatment induced tumor regression.
A total of 3 of her 10 lung metastases were resected to identify mutations expressed by the tumors, and these were found to express mutant KRAS G12D and HLA-C*08:02. The lymphocyte cultures that reacted most strongly against these antigens were expanded and made into a single infusion, which was administered after the patient had undergone nonmyeloablative conditioning using cyclophosphamide and fludarabine. The patient then received five doses of interleukin-2, which produced the only adverse effect of the entire regimen, fatigue.
At 40-day follow-up, all seven remaining lung metastases showed marked regression. One lesion showed progression at 9-month follow-up and was resected, and the patient has remained cancer free for the subsequent 4 months (N Engl J Med. 2016 Dec 8. doi:10.1056/NEJMoa1609279).
Laboratory analysis of the one metastasis that progressed showed that it had mutated further, losing heterozygosity of the copy of chromosome 6 that encoded HLA-C*08:02. “The presence of this molecule is required for direct tumor recognition by the transferred KRAS G12D-specific T cells. ... [Such a loss] has been observed in human cancers and may represent a hurdle that needs to be overcome to enhance immunotherapeutic efficacy in some patients,” Dr. Tran and his associates wrote.
“In such cases, targeting antigens that are presented by the remaining HLA class I alleles or exploiting the CD4+ T-cell response or the innate immune system against cancer may be necessary to induce a durable clinical response,” they added.
Adoptive transfer of cytotoxic T cells targeting a specific KRAS mutation (KRAS G12D) expressed by a metastatic colorectal cancer induced the regression of all seven lung metastases in a single patient, investigators report in the New England Journal of Medicine.
Mutations of the KRAS oncogene are frequent and drive the formation and progression of many human cancers. “The high incidence of KRAS G12D expression in [colorectal, pancreatic, and multiple other] cancers means that in the United States alone, thousands of patients per year would be potentially eligible for T-cell–based immunotherapy targeting KRAS G12D,” said Eric Tran, PhD, and his associates in the surgery branch, National Cancer Institute, Bethesda, Md.
They described the case of a 50-year-old woman participating in an ongoing phase II clinical trial assessing adoptive transfer of tumor-infiltrating lymphocytes targeting personalized cancer neoepitopes (individualized T-cell therapy). This patient was the only participant to date in whom the treatment induced tumor regression.
A total of 3 of her 10 lung metastases were resected to identify mutations expressed by the tumors, and these were found to express mutant KRAS G12D and HLA-C*08:02. The lymphocyte cultures that reacted most strongly against these antigens were expanded and made into a single infusion, which was administered after the patient had undergone nonmyeloablative conditioning using cyclophosphamide and fludarabine. The patient then received five doses of interleukin-2, which produced the only adverse effect of the entire regimen, fatigue.
At 40-day follow-up, all seven remaining lung metastases showed marked regression. One lesion showed progression at 9-month follow-up and was resected, and the patient has remained cancer free for the subsequent 4 months (N Engl J Med. 2016 Dec 8. doi:10.1056/NEJMoa1609279).
Laboratory analysis of the one metastasis that progressed showed that it had mutated further, losing heterozygosity of the copy of chromosome 6 that encoded HLA-C*08:02. “The presence of this molecule is required for direct tumor recognition by the transferred KRAS G12D-specific T cells. ... [Such a loss] has been observed in human cancers and may represent a hurdle that needs to be overcome to enhance immunotherapeutic efficacy in some patients,” Dr. Tran and his associates wrote.
“In such cases, targeting antigens that are presented by the remaining HLA class I alleles or exploiting the CD4+ T-cell response or the innate immune system against cancer may be necessary to induce a durable clinical response,” they added.
Adoptive transfer of cytotoxic T cells targeting a specific KRAS mutation (KRAS G12D) expressed by a metastatic colorectal cancer induced the regression of all seven lung metastases in a single patient, investigators report in the New England Journal of Medicine.
Mutations of the KRAS oncogene are frequent and drive the formation and progression of many human cancers. “The high incidence of KRAS G12D expression in [colorectal, pancreatic, and multiple other] cancers means that in the United States alone, thousands of patients per year would be potentially eligible for T-cell–based immunotherapy targeting KRAS G12D,” said Eric Tran, PhD, and his associates in the surgery branch, National Cancer Institute, Bethesda, Md.
They described the case of a 50-year-old woman participating in an ongoing phase II clinical trial assessing adoptive transfer of tumor-infiltrating lymphocytes targeting personalized cancer neoepitopes (individualized T-cell therapy). This patient was the only participant to date in whom the treatment induced tumor regression.
A total of 3 of her 10 lung metastases were resected to identify mutations expressed by the tumors, and these were found to express mutant KRAS G12D and HLA-C*08:02. The lymphocyte cultures that reacted most strongly against these antigens were expanded and made into a single infusion, which was administered after the patient had undergone nonmyeloablative conditioning using cyclophosphamide and fludarabine. The patient then received five doses of interleukin-2, which produced the only adverse effect of the entire regimen, fatigue.
At 40-day follow-up, all seven remaining lung metastases showed marked regression. One lesion showed progression at 9-month follow-up and was resected, and the patient has remained cancer free for the subsequent 4 months (N Engl J Med. 2016 Dec 8. doi:10.1056/NEJMoa1609279).
Laboratory analysis of the one metastasis that progressed showed that it had mutated further, losing heterozygosity of the copy of chromosome 6 that encoded HLA-C*08:02. “The presence of this molecule is required for direct tumor recognition by the transferred KRAS G12D-specific T cells. ... [Such a loss] has been observed in human cancers and may represent a hurdle that needs to be overcome to enhance immunotherapeutic efficacy in some patients,” Dr. Tran and his associates wrote.
“In such cases, targeting antigens that are presented by the remaining HLA class I alleles or exploiting the CD4+ T-cell response or the innate immune system against cancer may be necessary to induce a durable clinical response,” they added.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Adoptive transfer of cytotoxic T cells targeting a specific KRAS mutation expressed by a metastatic colorectal cancer induced the regression of all seven lung metastases in a single patient.
Major finding: At 40-day follow-up, all seven lung metastases showed marked regression; the single metastasis that showed progression at 9-month follow-up was resected, and the patient has remained cancer free for the subsequent 4 months.
Data source: A single case study involving a woman with metastatic colorectal cancer treated with a experimental immunotherapy and followed for 13 months.
Disclosures: This work was supported by the National Cancer Institute. Dr. Tran and some of his associates reported holding a pending patent related to anti-KRAS G12D T-cell receptors.