Lung Cancer

Real-world electronic health record data on tumor progression appears to be a good surrogate for overall survival, a finding that could help to improve estimates of benefit for complex cancer therapy regimens for use in both clinical trials and treatment planning, investigators say.

A study of electronic health record (EHR) data on more than 30,000 patients with non–small cell lung cancer (NSCLC) showed that real-world data on progression-free survival (PFS) showed a high degree of correlation with overall survival (OS), reported Sandra D. Griffith, PhD, of Flatiron Health, New York, and colleagues.

“As survival rates have improved and more than one therapy line has become typical, OS has become an inadequate metric for ascertaining the benefit of some cancer treatment interventions. Intermediate endpoints are essential for evaluating treatment benefits in real-world contexts. This study presents a scalable, feasible, and replicable approach to yield an EHR-generated progression variable ready for incorporation into large, contemporary real-world analyses,” they wrote in JCO Clinical Cancer Informatics.

The investigators studied retrospectively whether it would be feasible on a large scale to extract clinically relevant endpoints from an EHR-derived database that relies on technology-assisted abstraction of data from patient charts.

Their cohort included 30,276 patients diagnosed with advanced NSCLC from January 2011 through February 2018 who had two or more visits documented on EHR and who had been started on one or more lines of systemic therapy. Of this group, 16,606 had one or more documented tumor progression events, and 11,366 either died, discontinued therapy, or started on a new therapy.

The investigators found that among 20,000 evaluable patients, correlation of real-word PFS with OS was moderately high (Spearman’s P = .076), although for 11,902 patients with a progression event who died the correlation of EHR data with actual OS was somewhat lower (Spearman’s P = .069).

The strength of the correlations was verified in an duplicate random sample reviewed by independent abstractors.

The median time to abstract data on disease progression from individual electronic health records was 18 minutes.

“More work is needed to document how real-world progression under different treatments relates to treatment effects observed in clinical trials; understand the impact of different imaging and assessment cadences—for example, informative censoring; and clarify the relationship between real-world progression and other endpoints, such as real-world tumor response. Similar work is also needed in other tumor types,” Dr. Griffiths and colleagues wrote.

The study was supported by Flatiron Health, a subsidiary of Roche. Dr. Griffith and multiple co-authors are employees and stockholders of Flatiron Health and/or Roche.

SOURCE: Griffith SD et al. JCO Clinical Informatics. 2019 Aug 12. doi: 10.1200/CCI.19.00013.

Real-world electronic health record data on tumor progression appears to be a good surrogate for overall survival, a finding that could help to improve estimates of benefit for complex cancer therapy regimens for use in both clinical trials and treatment planning, investigators say.

A study of electronic health record (EHR) data on more than 30,000 patients with non–small cell lung cancer (NSCLC) showed that real-world data on progression-free survival (PFS) showed a high degree of correlation with overall survival (OS), reported Sandra D. Griffith, PhD, of Flatiron Health, New York, and colleagues.

“As survival rates have improved and more than one therapy line has become typical, OS has become an inadequate metric for ascertaining the benefit of some cancer treatment interventions. Intermediate endpoints are essential for evaluating treatment benefits in real-world contexts. This study presents a scalable, feasible, and replicable approach to yield an EHR-generated progression variable ready for incorporation into large, contemporary real-world analyses,” they wrote in JCO Clinical Cancer Informatics.

The investigators studied retrospectively whether it would be feasible on a large scale to extract clinically relevant endpoints from an EHR-derived database that relies on technology-assisted abstraction of data from patient charts.

Their cohort included 30,276 patients diagnosed with advanced NSCLC from January 2011 through February 2018 who had two or more visits documented on EHR and who had been started on one or more lines of systemic therapy. Of this group, 16,606 had one or more documented tumor progression events, and 11,366 either died, discontinued therapy, or started on a new therapy.

The investigators found that among 20,000 evaluable patients, correlation of real-word PFS with OS was moderately high (Spearman’s P = .076), although for 11,902 patients with a progression event who died the correlation of EHR data with actual OS was somewhat lower (Spearman’s P = .069).

The strength of the correlations was verified in an duplicate random sample reviewed by independent abstractors.

The median time to abstract data on disease progression from individual electronic health records was 18 minutes.

“More work is needed to document how real-world progression under different treatments relates to treatment effects observed in clinical trials; understand the impact of different imaging and assessment cadences—for example, informative censoring; and clarify the relationship between real-world progression and other endpoints, such as real-world tumor response. Similar work is also needed in other tumor types,” Dr. Griffiths and colleagues wrote.

The study was supported by Flatiron Health, a subsidiary of Roche. Dr. Griffith and multiple co-authors are employees and stockholders of Flatiron Health and/or Roche.

SOURCE: Griffith SD et al. JCO Clinical Informatics. 2019 Aug 12. doi: 10.1200/CCI.19.00013.

Real-world electronic health record data on tumor progression appears to be a good surrogate for overall survival, a finding that could help to improve estimates of benefit for complex cancer therapy regimens for use in both clinical trials and treatment planning, investigators say.

A study of electronic health record (EHR) data on more than 30,000 patients with non–small cell lung cancer (NSCLC) showed that real-world data on progression-free survival (PFS) showed a high degree of correlation with overall survival (OS), reported Sandra D. Griffith, PhD, of Flatiron Health, New York, and colleagues.

“As survival rates have improved and more than one therapy line has become typical, OS has become an inadequate metric for ascertaining the benefit of some cancer treatment interventions. Intermediate endpoints are essential for evaluating treatment benefits in real-world contexts. This study presents a scalable, feasible, and replicable approach to yield an EHR-generated progression variable ready for incorporation into large, contemporary real-world analyses,” they wrote in JCO Clinical Cancer Informatics.

The investigators studied retrospectively whether it would be feasible on a large scale to extract clinically relevant endpoints from an EHR-derived database that relies on technology-assisted abstraction of data from patient charts.

Their cohort included 30,276 patients diagnosed with advanced NSCLC from January 2011 through February 2018 who had two or more visits documented on EHR and who had been started on one or more lines of systemic therapy. Of this group, 16,606 had one or more documented tumor progression events, and 11,366 either died, discontinued therapy, or started on a new therapy.

The investigators found that among 20,000 evaluable patients, correlation of real-word PFS with OS was moderately high (Spearman’s P = .076), although for 11,902 patients with a progression event who died the correlation of EHR data with actual OS was somewhat lower (Spearman’s P = .069).

The strength of the correlations was verified in an duplicate random sample reviewed by independent abstractors.

The median time to abstract data on disease progression from individual electronic health records was 18 minutes.

“More work is needed to document how real-world progression under different treatments relates to treatment effects observed in clinical trials; understand the impact of different imaging and assessment cadences—for example, informative censoring; and clarify the relationship between real-world progression and other endpoints, such as real-world tumor response. Similar work is also needed in other tumor types,” Dr. Griffiths and colleagues wrote.

The study was supported by Flatiron Health, a subsidiary of Roche. Dr. Griffith and multiple co-authors are employees and stockholders of Flatiron Health and/or Roche.

SOURCE: Griffith SD et al. JCO Clinical Informatics. 2019 Aug 12. doi: 10.1200/CCI.19.00013.

In this edition of “How I will treat my next patient,” I examine the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement regarding screening for pancreatic cancer in normal-risk populations. I also review newly published information regarding low-dose CT screening (LDCT) for lung cancer in a commonly screened population – individuals with chronic obstructive pulmonary disease (COPD). Both publications highlight the complexity of implementing shared decision making in clinicians’ efforts to find these highly lethal cancers in their earliest, most curable stages.

Pancreatic cancer screening

In their recommendation, the USPSTF considered data relevant to the benefits and harms (exclusive of costs) of screening for pancreatic cancer in the 85%-90% of individuals who are at normal risk because they lack a known familial or genetic syndrome and do not have at least two affected relatives or one first-degree affected relative (JAMA. 2019;322[5]:438-44).

After reviewing 13 cohort studies employing image-based technologies (CT, MRI, endoscopic ultrasound) and biomarkers for screening, the USPSTF reaffirmed its 2004 recommendation against pancreatic cancer screening. They found no new evidence of sufficient strength and quality to alter their previous “D grade” for screening (i.e., “Don’t do it.”). There were at least moderate harms of screening and subsequent treatment in normal-risk populations. These recommendations apply to asymptomatic individuals with new-onset diabetes mellitus, smokers, older adults, obese patients, and patients with a history of chronic pancreatitis.

What this means in practice

In the nicely written and comprehensive recommendation statement and in the two accompanying editorials (JAMA Surg. 2019 Aug 6. doi: 10.1001/jamasurg.2019.2832; JAMA. 2019;322[5]:407-8), the authors were explicit that the “D grade” for pancreatic cancer screening did not apply to individuals from familial pancreatic cancer kindreds and those with germline mutations and Lynch syndrome mismatch repair genes. For them, the relative risk of pancreatic cancer (greater than 5%) may justify the morbidity of available surveillance technologies, especially since U.S. and International screening studies in these high-risk individuals have generated data suggesting a benefit for treatment of screen-detected cancers.

The USPSTF and the editorial authors were strongly supportive of, and enthusiastic about, ongoing research efforts. Recently, a joint effort at the National Institutes of Health began recruiting centers for a study to assess the sensitivity of novel biomarkers in detecting pancreatic cancer among adults with new-onset diabetes (A211701).

To me, it is clear that the pathway to identifying effective screening for pancreatic cancer – which is forecast to become the second leading cause of cancer death in the United States by 2020 – will focus on high-risk populations first, enabling accurate determination of sensitivity and specificity before being applied to the general population. This is as it should be.
 

Lung cancer screening

Currently, guidelines from the National Comprehensive Cancer Network recommend LDCT screening annually for high-risk smokers, former smokers, and individuals with additional risk factors aged 55-77 years. The National Lung Screening Trial indicated that LDCT screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in a similar population. NCCN guidelines stress the importance of shared decision making and include a table of risks and benefits that should be considered.

Jonathan M. Iaccarino, MD, and colleagues quantified the risks of screening among COPD patients in a secondary analysis of the more than 75,000 LDCT scans that were performed among the more than 26,000 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016). In comparison with participants who did not self-report a diagnosis of COPD, the 4,632 participants with self-reported COPD were significantly more likely to require further diagnostic studies, have an invasive procedure, have a complication of any type from the invasive procedure, and suffer a serious complication. The establishment of a lung cancer diagnosis from the invasive procedure, however, occurred in just 6.1% of COPD patients versus 3.6% of patients without COPD.

What this means in practice

At a consensus conference convened by the National Quality Forum, shared decision making was defined as a process of communication in which clinicians and patients work together to make decisions that align with what matters most to patients. Ideally, shared decision making requires clear, accurate, unbiased medical evidence about reasonable alternatives; tailored evidence for individual patients; and the incorporation of patient values, goals, informed preferences and concerns, including a discussion of treatment burdens. All of us wrestle with the challenge of conducting these conversations in a comprehensive and unbiased manner. I am not sure that I have ever achieved an ideal shared decision-making conversation in my practice.

Despite the limitations acknowledged by the authors – self-reported diagnosis of COPD, outcomes that were not the primary focus of the trial, failure to incorporate other important comorbid conditions – the study by Dr. Iaccarino and colleagues helps to quantify risks and benefits for a commonly screened population, specifically COPD patients. Most importantly, it focuses our attention on the key goal of all cancer-screening efforts – applying our personal and technological resources to patients who benefit the most and will suffer the least harm from our efforts.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I examine the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement regarding screening for pancreatic cancer in normal-risk populations. I also review newly published information regarding low-dose CT screening (LDCT) for lung cancer in a commonly screened population – individuals with chronic obstructive pulmonary disease (COPD). Both publications highlight the complexity of implementing shared decision making in clinicians’ efforts to find these highly lethal cancers in their earliest, most curable stages.

Pancreatic cancer screening

In their recommendation, the USPSTF considered data relevant to the benefits and harms (exclusive of costs) of screening for pancreatic cancer in the 85%-90% of individuals who are at normal risk because they lack a known familial or genetic syndrome and do not have at least two affected relatives or one first-degree affected relative (JAMA. 2019;322[5]:438-44).

After reviewing 13 cohort studies employing image-based technologies (CT, MRI, endoscopic ultrasound) and biomarkers for screening, the USPSTF reaffirmed its 2004 recommendation against pancreatic cancer screening. They found no new evidence of sufficient strength and quality to alter their previous “D grade” for screening (i.e., “Don’t do it.”). There were at least moderate harms of screening and subsequent treatment in normal-risk populations. These recommendations apply to asymptomatic individuals with new-onset diabetes mellitus, smokers, older adults, obese patients, and patients with a history of chronic pancreatitis.

What this means in practice

In the nicely written and comprehensive recommendation statement and in the two accompanying editorials (JAMA Surg. 2019 Aug 6. doi: 10.1001/jamasurg.2019.2832; JAMA. 2019;322[5]:407-8), the authors were explicit that the “D grade” for pancreatic cancer screening did not apply to individuals from familial pancreatic cancer kindreds and those with germline mutations and Lynch syndrome mismatch repair genes. For them, the relative risk of pancreatic cancer (greater than 5%) may justify the morbidity of available surveillance technologies, especially since U.S. and International screening studies in these high-risk individuals have generated data suggesting a benefit for treatment of screen-detected cancers.

The USPSTF and the editorial authors were strongly supportive of, and enthusiastic about, ongoing research efforts. Recently, a joint effort at the National Institutes of Health began recruiting centers for a study to assess the sensitivity of novel biomarkers in detecting pancreatic cancer among adults with new-onset diabetes (A211701).

To me, it is clear that the pathway to identifying effective screening for pancreatic cancer – which is forecast to become the second leading cause of cancer death in the United States by 2020 – will focus on high-risk populations first, enabling accurate determination of sensitivity and specificity before being applied to the general population. This is as it should be.
 

Lung cancer screening

Currently, guidelines from the National Comprehensive Cancer Network recommend LDCT screening annually for high-risk smokers, former smokers, and individuals with additional risk factors aged 55-77 years. The National Lung Screening Trial indicated that LDCT screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in a similar population. NCCN guidelines stress the importance of shared decision making and include a table of risks and benefits that should be considered.

Jonathan M. Iaccarino, MD, and colleagues quantified the risks of screening among COPD patients in a secondary analysis of the more than 75,000 LDCT scans that were performed among the more than 26,000 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016). In comparison with participants who did not self-report a diagnosis of COPD, the 4,632 participants with self-reported COPD were significantly more likely to require further diagnostic studies, have an invasive procedure, have a complication of any type from the invasive procedure, and suffer a serious complication. The establishment of a lung cancer diagnosis from the invasive procedure, however, occurred in just 6.1% of COPD patients versus 3.6% of patients without COPD.

What this means in practice

At a consensus conference convened by the National Quality Forum, shared decision making was defined as a process of communication in which clinicians and patients work together to make decisions that align with what matters most to patients. Ideally, shared decision making requires clear, accurate, unbiased medical evidence about reasonable alternatives; tailored evidence for individual patients; and the incorporation of patient values, goals, informed preferences and concerns, including a discussion of treatment burdens. All of us wrestle with the challenge of conducting these conversations in a comprehensive and unbiased manner. I am not sure that I have ever achieved an ideal shared decision-making conversation in my practice.

Despite the limitations acknowledged by the authors – self-reported diagnosis of COPD, outcomes that were not the primary focus of the trial, failure to incorporate other important comorbid conditions – the study by Dr. Iaccarino and colleagues helps to quantify risks and benefits for a commonly screened population, specifically COPD patients. Most importantly, it focuses our attention on the key goal of all cancer-screening efforts – applying our personal and technological resources to patients who benefit the most and will suffer the least harm from our efforts.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I examine the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement regarding screening for pancreatic cancer in normal-risk populations. I also review newly published information regarding low-dose CT screening (LDCT) for lung cancer in a commonly screened population – individuals with chronic obstructive pulmonary disease (COPD). Both publications highlight the complexity of implementing shared decision making in clinicians’ efforts to find these highly lethal cancers in their earliest, most curable stages.

Pancreatic cancer screening

In their recommendation, the USPSTF considered data relevant to the benefits and harms (exclusive of costs) of screening for pancreatic cancer in the 85%-90% of individuals who are at normal risk because they lack a known familial or genetic syndrome and do not have at least two affected relatives or one first-degree affected relative (JAMA. 2019;322[5]:438-44).

After reviewing 13 cohort studies employing image-based technologies (CT, MRI, endoscopic ultrasound) and biomarkers for screening, the USPSTF reaffirmed its 2004 recommendation against pancreatic cancer screening. They found no new evidence of sufficient strength and quality to alter their previous “D grade” for screening (i.e., “Don’t do it.”). There were at least moderate harms of screening and subsequent treatment in normal-risk populations. These recommendations apply to asymptomatic individuals with new-onset diabetes mellitus, smokers, older adults, obese patients, and patients with a history of chronic pancreatitis.

What this means in practice

In the nicely written and comprehensive recommendation statement and in the two accompanying editorials (JAMA Surg. 2019 Aug 6. doi: 10.1001/jamasurg.2019.2832; JAMA. 2019;322[5]:407-8), the authors were explicit that the “D grade” for pancreatic cancer screening did not apply to individuals from familial pancreatic cancer kindreds and those with germline mutations and Lynch syndrome mismatch repair genes. For them, the relative risk of pancreatic cancer (greater than 5%) may justify the morbidity of available surveillance technologies, especially since U.S. and International screening studies in these high-risk individuals have generated data suggesting a benefit for treatment of screen-detected cancers.

The USPSTF and the editorial authors were strongly supportive of, and enthusiastic about, ongoing research efforts. Recently, a joint effort at the National Institutes of Health began recruiting centers for a study to assess the sensitivity of novel biomarkers in detecting pancreatic cancer among adults with new-onset diabetes (A211701).

To me, it is clear that the pathway to identifying effective screening for pancreatic cancer – which is forecast to become the second leading cause of cancer death in the United States by 2020 – will focus on high-risk populations first, enabling accurate determination of sensitivity and specificity before being applied to the general population. This is as it should be.
 

Lung cancer screening

Currently, guidelines from the National Comprehensive Cancer Network recommend LDCT screening annually for high-risk smokers, former smokers, and individuals with additional risk factors aged 55-77 years. The National Lung Screening Trial indicated that LDCT screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in a similar population. NCCN guidelines stress the importance of shared decision making and include a table of risks and benefits that should be considered.

Jonathan M. Iaccarino, MD, and colleagues quantified the risks of screening among COPD patients in a secondary analysis of the more than 75,000 LDCT scans that were performed among the more than 26,000 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016). In comparison with participants who did not self-report a diagnosis of COPD, the 4,632 participants with self-reported COPD were significantly more likely to require further diagnostic studies, have an invasive procedure, have a complication of any type from the invasive procedure, and suffer a serious complication. The establishment of a lung cancer diagnosis from the invasive procedure, however, occurred in just 6.1% of COPD patients versus 3.6% of patients without COPD.

What this means in practice

At a consensus conference convened by the National Quality Forum, shared decision making was defined as a process of communication in which clinicians and patients work together to make decisions that align with what matters most to patients. Ideally, shared decision making requires clear, accurate, unbiased medical evidence about reasonable alternatives; tailored evidence for individual patients; and the incorporation of patient values, goals, informed preferences and concerns, including a discussion of treatment burdens. All of us wrestle with the challenge of conducting these conversations in a comprehensive and unbiased manner. I am not sure that I have ever achieved an ideal shared decision-making conversation in my practice.

Despite the limitations acknowledged by the authors – self-reported diagnosis of COPD, outcomes that were not the primary focus of the trial, failure to incorporate other important comorbid conditions – the study by Dr. Iaccarino and colleagues helps to quantify risks and benefits for a commonly screened population, specifically COPD patients. Most importantly, it focuses our attention on the key goal of all cancer-screening efforts – applying our personal and technological resources to patients who benefit the most and will suffer the least harm from our efforts.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

Rozlytrek (entrectinib) has been approved to treat cancers with neurotrophic tyrosine receptor kinase (NTRK) gene fusion defects in adults and adolescents for whom there are no effective treatments, the Food and Drug Administration announced in a press release.

Olivier Le Moal/Getty Images

Entrectinib was also approved for the treatment of adults with metastatic non–small cell lung cancers that are ROS1-positive.

“We are in an exciting era of innovation in cancer treatment as we continue to see development in tissue-agnostic therapies, which have the potential to transform cancer treatment. We’re seeing continued advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine,” FDA Acting Commissioner Ned Sharpless, MD, said in the release.

This is the third time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than on the original tumor’s location. The previous tissue-agnostic indications approved by the FDA were pembrolizumab (Keytruda) for tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in 2017 and larotrectinib (Vitrakvi) for NTRK gene fusion tumors in 2018.

The approval of entrectinib was granted to Genentech. “Rozlytrek is the first FDA-approved treatment that selectively targets both ROS1 and NTRK fusions, and, importantly, has also shown responses in these rare cancer types that have spread to the brain,” Sandra Horning, MD, chief medical officer and head of global product development for Genentech, said in a separate press release.

Foundation Medicine will submit Foundation One CDx to the FDA for approval as a companion diagnostic for entrectinib, according to the Genentech release; an FDA-approved companion diagnostic for entrectinib is not available at this time.

“Today’s approval includes an indication for pediatric patients, 12 years of age and older, who have NTRK fusion–positive tumors by relying on efficacy information obtained primarily in adults,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Efficacy in adolescents was derived from adult data and safety was demonstrated in 30 pediatric patients.”

Entrectinib was evaluated in four clinical trials that included 54 adults with NTRK fusion–positive tumors. The overall response rate was 57%, with 7.4% of patients having complete disappearance of the tumor. Among the 31 patients with tumor shrinkage, 61% had tumor shrinkage persist for 9 months or longer. The most common cancer locations were the lung, salivary gland, breast, thyroid, and colon/rectum.

Clinical studies evaluated 51 adults with ROS1-positive lung cancer. The overall response rate was 78%, with 5.9% of patients having complete disappearance of their cancer. Among the 40 patients with tumor shrinkage, 55% had tumor shrinkage persist for 12 months or longer.

The most serious side effects of entrectinib are heart failure, central nervous system effects, changes in sleep pattern, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, and vision disorders. Females of reproductive age and males with a female partner of reproductive potential are advised to use effective contraception during treatment; the drug may cause harm to a developing fetus or newborn baby.

Genentech must provide additional clinical trial data to the FDA as a condition of the approval.

mdales@mdedge.com

Rozlytrek (entrectinib) has been approved to treat cancers with neurotrophic tyrosine receptor kinase (NTRK) gene fusion defects in adults and adolescents for whom there are no effective treatments, the Food and Drug Administration announced in a press release.

Olivier Le Moal/Getty Images

Entrectinib was also approved for the treatment of adults with metastatic non–small cell lung cancers that are ROS1-positive.

“We are in an exciting era of innovation in cancer treatment as we continue to see development in tissue-agnostic therapies, which have the potential to transform cancer treatment. We’re seeing continued advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine,” FDA Acting Commissioner Ned Sharpless, MD, said in the release.

This is the third time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than on the original tumor’s location. The previous tissue-agnostic indications approved by the FDA were pembrolizumab (Keytruda) for tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in 2017 and larotrectinib (Vitrakvi) for NTRK gene fusion tumors in 2018.

The approval of entrectinib was granted to Genentech. “Rozlytrek is the first FDA-approved treatment that selectively targets both ROS1 and NTRK fusions, and, importantly, has also shown responses in these rare cancer types that have spread to the brain,” Sandra Horning, MD, chief medical officer and head of global product development for Genentech, said in a separate press release.

Foundation Medicine will submit Foundation One CDx to the FDA for approval as a companion diagnostic for entrectinib, according to the Genentech release; an FDA-approved companion diagnostic for entrectinib is not available at this time.

“Today’s approval includes an indication for pediatric patients, 12 years of age and older, who have NTRK fusion–positive tumors by relying on efficacy information obtained primarily in adults,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Efficacy in adolescents was derived from adult data and safety was demonstrated in 30 pediatric patients.”

Entrectinib was evaluated in four clinical trials that included 54 adults with NTRK fusion–positive tumors. The overall response rate was 57%, with 7.4% of patients having complete disappearance of the tumor. Among the 31 patients with tumor shrinkage, 61% had tumor shrinkage persist for 9 months or longer. The most common cancer locations were the lung, salivary gland, breast, thyroid, and colon/rectum.

Clinical studies evaluated 51 adults with ROS1-positive lung cancer. The overall response rate was 78%, with 5.9% of patients having complete disappearance of their cancer. Among the 40 patients with tumor shrinkage, 55% had tumor shrinkage persist for 12 months or longer.

The most serious side effects of entrectinib are heart failure, central nervous system effects, changes in sleep pattern, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, and vision disorders. Females of reproductive age and males with a female partner of reproductive potential are advised to use effective contraception during treatment; the drug may cause harm to a developing fetus or newborn baby.

Genentech must provide additional clinical trial data to the FDA as a condition of the approval.

mdales@mdedge.com

Rozlytrek (entrectinib) has been approved to treat cancers with neurotrophic tyrosine receptor kinase (NTRK) gene fusion defects in adults and adolescents for whom there are no effective treatments, the Food and Drug Administration announced in a press release.

Olivier Le Moal/Getty Images

Entrectinib was also approved for the treatment of adults with metastatic non–small cell lung cancers that are ROS1-positive.

“We are in an exciting era of innovation in cancer treatment as we continue to see development in tissue-agnostic therapies, which have the potential to transform cancer treatment. We’re seeing continued advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine,” FDA Acting Commissioner Ned Sharpless, MD, said in the release.

This is the third time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than on the original tumor’s location. The previous tissue-agnostic indications approved by the FDA were pembrolizumab (Keytruda) for tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in 2017 and larotrectinib (Vitrakvi) for NTRK gene fusion tumors in 2018.

The approval of entrectinib was granted to Genentech. “Rozlytrek is the first FDA-approved treatment that selectively targets both ROS1 and NTRK fusions, and, importantly, has also shown responses in these rare cancer types that have spread to the brain,” Sandra Horning, MD, chief medical officer and head of global product development for Genentech, said in a separate press release.

Foundation Medicine will submit Foundation One CDx to the FDA for approval as a companion diagnostic for entrectinib, according to the Genentech release; an FDA-approved companion diagnostic for entrectinib is not available at this time.

“Today’s approval includes an indication for pediatric patients, 12 years of age and older, who have NTRK fusion–positive tumors by relying on efficacy information obtained primarily in adults,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Efficacy in adolescents was derived from adult data and safety was demonstrated in 30 pediatric patients.”

Entrectinib was evaluated in four clinical trials that included 54 adults with NTRK fusion–positive tumors. The overall response rate was 57%, with 7.4% of patients having complete disappearance of the tumor. Among the 31 patients with tumor shrinkage, 61% had tumor shrinkage persist for 9 months or longer. The most common cancer locations were the lung, salivary gland, breast, thyroid, and colon/rectum.

Clinical studies evaluated 51 adults with ROS1-positive lung cancer. The overall response rate was 78%, with 5.9% of patients having complete disappearance of their cancer. Among the 40 patients with tumor shrinkage, 55% had tumor shrinkage persist for 12 months or longer.

The most serious side effects of entrectinib are heart failure, central nervous system effects, changes in sleep pattern, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, and vision disorders. Females of reproductive age and males with a female partner of reproductive potential are advised to use effective contraception during treatment; the drug may cause harm to a developing fetus or newborn baby.

Genentech must provide additional clinical trial data to the FDA as a condition of the approval.

mdales@mdedge.com

A nationwide survey of radiation oncologists showed a decline in the use of prophylactic cranial irradiation (PCI) for extensive-stage small cell lung cancer (ES-SCLC) after the release of phase 3 study results by Takahashi et al.

The recent study by Toshiaki Takahashi, MD, and colleagues (Lancet Oncol. 2017;18[5]:663-71) demonstrated no overall survival benefit when comparing active magnetic resonance imaging surveillance with PCI in patients with ES-SCLC. The results challenged the formerly accepted belief of the benefit of PCI for patients with ES-SCLC.

“We conducted a nationwide survey study of radiation oncologists to assess changes in the use of PCI for patients with ES-SCLC following publication of the trial by Takahashi et al.,” wrote Olsi Gjyshi, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in a research letter published in JAMA Network Open.

Dr. Gjyshi and colleagues distributed the anonymous survey to 3,851 United States–based radiation oncologists registered with the American Society for Radiation Oncology (ASTRO). In total, 487 members (12.6%) completed the survey.

After analysis, the researchers found that 72% of respondents regularly offered PCI to patients before the publication of the study by Takahashi et al., while only 44% do so currently (difference, 28%; 95% confidence interval, 25%-31%; P less than .001).

With respect to radiation oncologists in private versus academic settings, no significant difference in practice patterns was observed (P = .71).

“Regression analysis showed no difference in likelihood of offering PCI based on practice setting, location, or size; volume of patients treated for lung cancer; or years in practice,” the researchers wrote.

In respondents unaware of the Takahashi et al. study, 85% continued to propose PCI, which was greater than those aware of the trial (odds ratio, 0.11; 95% CI, 0.04-0.32; P less than .001).

The researchers acknowledged a key limitation of the study was that radiation oncologists familiar with the study by Dr. Takahashi and colleagues may have been more apt to respond to the survey. As a result, participation bias could have influenced the results.

“These results highlight the continued lack of consensus for PCI in SCLC and support ongoing investigations,” they concluded.

No funding sources were reported. One co-author reported financial affiliations with Novocure, Inc. The other authors reported no conflicts of interest.

SOURCE: Gjyshi O et al. JAMA Netw Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9135.

A nationwide survey of radiation oncologists showed a decline in the use of prophylactic cranial irradiation (PCI) for extensive-stage small cell lung cancer (ES-SCLC) after the release of phase 3 study results by Takahashi et al.

The recent study by Toshiaki Takahashi, MD, and colleagues (Lancet Oncol. 2017;18[5]:663-71) demonstrated no overall survival benefit when comparing active magnetic resonance imaging surveillance with PCI in patients with ES-SCLC. The results challenged the formerly accepted belief of the benefit of PCI for patients with ES-SCLC.

“We conducted a nationwide survey study of radiation oncologists to assess changes in the use of PCI for patients with ES-SCLC following publication of the trial by Takahashi et al.,” wrote Olsi Gjyshi, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in a research letter published in JAMA Network Open.

Dr. Gjyshi and colleagues distributed the anonymous survey to 3,851 United States–based radiation oncologists registered with the American Society for Radiation Oncology (ASTRO). In total, 487 members (12.6%) completed the survey.

After analysis, the researchers found that 72% of respondents regularly offered PCI to patients before the publication of the study by Takahashi et al., while only 44% do so currently (difference, 28%; 95% confidence interval, 25%-31%; P less than .001).

With respect to radiation oncologists in private versus academic settings, no significant difference in practice patterns was observed (P = .71).

“Regression analysis showed no difference in likelihood of offering PCI based on practice setting, location, or size; volume of patients treated for lung cancer; or years in practice,” the researchers wrote.

In respondents unaware of the Takahashi et al. study, 85% continued to propose PCI, which was greater than those aware of the trial (odds ratio, 0.11; 95% CI, 0.04-0.32; P less than .001).

The researchers acknowledged a key limitation of the study was that radiation oncologists familiar with the study by Dr. Takahashi and colleagues may have been more apt to respond to the survey. As a result, participation bias could have influenced the results.

“These results highlight the continued lack of consensus for PCI in SCLC and support ongoing investigations,” they concluded.

No funding sources were reported. One co-author reported financial affiliations with Novocure, Inc. The other authors reported no conflicts of interest.

SOURCE: Gjyshi O et al. JAMA Netw Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9135.

A nationwide survey of radiation oncologists showed a decline in the use of prophylactic cranial irradiation (PCI) for extensive-stage small cell lung cancer (ES-SCLC) after the release of phase 3 study results by Takahashi et al.

The recent study by Toshiaki Takahashi, MD, and colleagues (Lancet Oncol. 2017;18[5]:663-71) demonstrated no overall survival benefit when comparing active magnetic resonance imaging surveillance with PCI in patients with ES-SCLC. The results challenged the formerly accepted belief of the benefit of PCI for patients with ES-SCLC.

“We conducted a nationwide survey study of radiation oncologists to assess changes in the use of PCI for patients with ES-SCLC following publication of the trial by Takahashi et al.,” wrote Olsi Gjyshi, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in a research letter published in JAMA Network Open.

Dr. Gjyshi and colleagues distributed the anonymous survey to 3,851 United States–based radiation oncologists registered with the American Society for Radiation Oncology (ASTRO). In total, 487 members (12.6%) completed the survey.

After analysis, the researchers found that 72% of respondents regularly offered PCI to patients before the publication of the study by Takahashi et al., while only 44% do so currently (difference, 28%; 95% confidence interval, 25%-31%; P less than .001).

With respect to radiation oncologists in private versus academic settings, no significant difference in practice patterns was observed (P = .71).

“Regression analysis showed no difference in likelihood of offering PCI based on practice setting, location, or size; volume of patients treated for lung cancer; or years in practice,” the researchers wrote.

In respondents unaware of the Takahashi et al. study, 85% continued to propose PCI, which was greater than those aware of the trial (odds ratio, 0.11; 95% CI, 0.04-0.32; P less than .001).

The researchers acknowledged a key limitation of the study was that radiation oncologists familiar with the study by Dr. Takahashi and colleagues may have been more apt to respond to the survey. As a result, participation bias could have influenced the results.

“These results highlight the continued lack of consensus for PCI in SCLC and support ongoing investigations,” they concluded.

No funding sources were reported. One co-author reported financial affiliations with Novocure, Inc. The other authors reported no conflicts of interest.

SOURCE: Gjyshi O et al. JAMA Netw Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9135.

Next-generation sequencing (NGS) of tumor samples seldom changes patient management, and even when it does prompt off-label therapy, outcomes are usually poor, one center’s experience suggests.

“NGS has allowed more personalized medicine in oncology. It is well established that treatment of certain actionable mutations improves outcomes in many cancer types,” wrote Gregory J. Kubicek, MD, of MD Anderson Cancer Center at Cooper in Camden, N.J., and colleagues.

However, evidence of its utility to date has been mixed, and key trials – NCI-MPACT (National Cancer Institute Molecular Profiling–Based Assignment of Cancer Therapy) and NCI-MATCH (National Cancer Institute Molecular Analysis for Therapy Choice)—are still ongoing. “In the interim, the oncologist must make clinical decisions with limited empiric data but an exponentially increasing number of options,” they noted.

The investigators studied outcomes of the first 305 consecutive patients at their institution for whom tissue samples were sent to FoundationOne for NGS testing between March 2014 and April 2017. On average, the patients had received two lines of therapy, and the test was ordered 1.1 years from diagnosis of metastatic disease.

Study findings reported in the Journal of Oncology Practice showed that 116 of the tests were unusable because they did not yield a report (most often as a result of insufficient tissue) or yielded a report that could not be acted on owing to follow-up issues (patient loss of contact, transfer to hospice, or death).

Of the 189 potentially usable tests, 40.2% and 66.7% showed an aberration targetable by on-label therapies and off-label therapies, respectively. And fully 89.9% had actionable aberrations via all potential avenues, including clinical trials.

However, only 11.1% of the 189 potentially usable tests (and merely 8.3% of 253 completed tests and 6.9% of all 305 ordered tests) yielded a change in management, including use of on-label or off-label therapies, enrollment in clinical trials, or discontinuation of medications with a predicted poor response.

Of the six patients who were started on an off-label therapy, the median duration of treatment was 46 days, with half of these patients each stopping therapy because of death or because of progression.

“A vast majority of NGS assay results were not actively incorporated into clinical decision making, despite many assays indicating potential on- or off-label therapies,” Dr. Kubicek and coinvestigators wrote. “Given the escalating cost of medical care and scrutiny thereof, it is important to analyze whether tests are changing management and order tests appropriately.”

Several factors may explain the observed low use of NGS test results, they noted. For example, many patients were heavily pretreated, so some NGS-detected mutations would have already been known. Also, clinicians at the center had little experience with NGS testing.

“A variety of factors make precisely defining the utility of these assays in clinical decision making difficult, but we can certainly conclude that we have observed substantial costs with few discernible benefits,” the investigators stated. “It is possible that there will be greater use in the future as familiarity with these assays increases. Similarly, although we found poor outcomes with NGS-directed off-label therapies, we will eagerly await the results of NCI-MPACT and NCI-MATCH.”

Dr. Kubicek disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Davis W et al. J Oncol Pract. 2019 Aug 2. doi: 10.1200/JOP.19.00269.

Next-generation sequencing (NGS) of tumor samples seldom changes patient management, and even when it does prompt off-label therapy, outcomes are usually poor, one center’s experience suggests.

“NGS has allowed more personalized medicine in oncology. It is well established that treatment of certain actionable mutations improves outcomes in many cancer types,” wrote Gregory J. Kubicek, MD, of MD Anderson Cancer Center at Cooper in Camden, N.J., and colleagues.

However, evidence of its utility to date has been mixed, and key trials – NCI-MPACT (National Cancer Institute Molecular Profiling–Based Assignment of Cancer Therapy) and NCI-MATCH (National Cancer Institute Molecular Analysis for Therapy Choice)—are still ongoing. “In the interim, the oncologist must make clinical decisions with limited empiric data but an exponentially increasing number of options,” they noted.

The investigators studied outcomes of the first 305 consecutive patients at their institution for whom tissue samples were sent to FoundationOne for NGS testing between March 2014 and April 2017. On average, the patients had received two lines of therapy, and the test was ordered 1.1 years from diagnosis of metastatic disease.

Study findings reported in the Journal of Oncology Practice showed that 116 of the tests were unusable because they did not yield a report (most often as a result of insufficient tissue) or yielded a report that could not be acted on owing to follow-up issues (patient loss of contact, transfer to hospice, or death).

Of the 189 potentially usable tests, 40.2% and 66.7% showed an aberration targetable by on-label therapies and off-label therapies, respectively. And fully 89.9% had actionable aberrations via all potential avenues, including clinical trials.

However, only 11.1% of the 189 potentially usable tests (and merely 8.3% of 253 completed tests and 6.9% of all 305 ordered tests) yielded a change in management, including use of on-label or off-label therapies, enrollment in clinical trials, or discontinuation of medications with a predicted poor response.

Of the six patients who were started on an off-label therapy, the median duration of treatment was 46 days, with half of these patients each stopping therapy because of death or because of progression.

“A vast majority of NGS assay results were not actively incorporated into clinical decision making, despite many assays indicating potential on- or off-label therapies,” Dr. Kubicek and coinvestigators wrote. “Given the escalating cost of medical care and scrutiny thereof, it is important to analyze whether tests are changing management and order tests appropriately.”

Several factors may explain the observed low use of NGS test results, they noted. For example, many patients were heavily pretreated, so some NGS-detected mutations would have already been known. Also, clinicians at the center had little experience with NGS testing.

“A variety of factors make precisely defining the utility of these assays in clinical decision making difficult, but we can certainly conclude that we have observed substantial costs with few discernible benefits,” the investigators stated. “It is possible that there will be greater use in the future as familiarity with these assays increases. Similarly, although we found poor outcomes with NGS-directed off-label therapies, we will eagerly await the results of NCI-MPACT and NCI-MATCH.”

Dr. Kubicek disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Davis W et al. J Oncol Pract. 2019 Aug 2. doi: 10.1200/JOP.19.00269.

Next-generation sequencing (NGS) of tumor samples seldom changes patient management, and even when it does prompt off-label therapy, outcomes are usually poor, one center’s experience suggests.

“NGS has allowed more personalized medicine in oncology. It is well established that treatment of certain actionable mutations improves outcomes in many cancer types,” wrote Gregory J. Kubicek, MD, of MD Anderson Cancer Center at Cooper in Camden, N.J., and colleagues.

However, evidence of its utility to date has been mixed, and key trials – NCI-MPACT (National Cancer Institute Molecular Profiling–Based Assignment of Cancer Therapy) and NCI-MATCH (National Cancer Institute Molecular Analysis for Therapy Choice)—are still ongoing. “In the interim, the oncologist must make clinical decisions with limited empiric data but an exponentially increasing number of options,” they noted.

The investigators studied outcomes of the first 305 consecutive patients at their institution for whom tissue samples were sent to FoundationOne for NGS testing between March 2014 and April 2017. On average, the patients had received two lines of therapy, and the test was ordered 1.1 years from diagnosis of metastatic disease.

Study findings reported in the Journal of Oncology Practice showed that 116 of the tests were unusable because they did not yield a report (most often as a result of insufficient tissue) or yielded a report that could not be acted on owing to follow-up issues (patient loss of contact, transfer to hospice, or death).

Of the 189 potentially usable tests, 40.2% and 66.7% showed an aberration targetable by on-label therapies and off-label therapies, respectively. And fully 89.9% had actionable aberrations via all potential avenues, including clinical trials.

However, only 11.1% of the 189 potentially usable tests (and merely 8.3% of 253 completed tests and 6.9% of all 305 ordered tests) yielded a change in management, including use of on-label or off-label therapies, enrollment in clinical trials, or discontinuation of medications with a predicted poor response.

Of the six patients who were started on an off-label therapy, the median duration of treatment was 46 days, with half of these patients each stopping therapy because of death or because of progression.

“A vast majority of NGS assay results were not actively incorporated into clinical decision making, despite many assays indicating potential on- or off-label therapies,” Dr. Kubicek and coinvestigators wrote. “Given the escalating cost of medical care and scrutiny thereof, it is important to analyze whether tests are changing management and order tests appropriately.”

Several factors may explain the observed low use of NGS test results, they noted. For example, many patients were heavily pretreated, so some NGS-detected mutations would have already been known. Also, clinicians at the center had little experience with NGS testing.

“A variety of factors make precisely defining the utility of these assays in clinical decision making difficult, but we can certainly conclude that we have observed substantial costs with few discernible benefits,” the investigators stated. “It is possible that there will be greater use in the future as familiarity with these assays increases. Similarly, although we found poor outcomes with NGS-directed off-label therapies, we will eagerly await the results of NCI-MPACT and NCI-MATCH.”

Dr. Kubicek disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Davis W et al. J Oncol Pract. 2019 Aug 2. doi: 10.1200/JOP.19.00269.

Addition of bevacizumab to erlotinib, the standard first-line therapy, failed to improve outcomes in patients with advanced epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC), according to a multicenter, phase 2, randomized, controlled trial.

“The development of erlotinib as a first-line therapy was an important advance, but there was interest in improving the efficacy of erlotinib,” noted the investigators, led by Thomas E. Stinchcombe, MD, of the Duke Cancer Institute in Durham, N.C. Preclinical data suggested that adding an antiangiogenic agent could overcome resistance, and subgroup analyses of a phase 3 trial hinted at greater efficacy of this combination in patients with EGFR-mutant disease (Lancet. 2011;377:1846-54).

The new trial was conducted among 88 patients with previously untreated stage 4 EGFR-mutant NSCLC eligible to receive bevacizumab. Two-thirds had an EGFR exon 19 deletion.

The patients were assigned evenly to receive erlotinib (Tarceva), an EGFR tyrosine kinase inhibitor, either alone or in combination with bevacizumab (Avastin), an antibody directed against vascular endothelial growth factor.

Results reported in JAMA Oncology showed that, during a median follow-up of 33 months, median progression-free survival (PFS) – the trial’s primary endpoint – was 17.9 months with the combination and 13.5 months with erlotinib alone, a nonsignificant difference (hazard ratio, 0.81; P = .39).

There was also no significant difference between groups in objective response rate (81% vs. 83%; P = .81) and overall survival (median, 32.4 vs. 50.6 months; HR, 1.41; P = .33).

Relative to the erlotinib monotherapy group, the combination therapy group had higher rates of grade 3 or worse acneiform rash (26% vs. 16%), hypertension (40% vs. 20%), and proteinuria (12% vs. 0%), but a lower rate of grade 3 or worse diarrhea (9% vs. 13%).

“Our study, unlike previous randomized clinical trials, did not reveal a significant improvement in PFS with the combination of erlotinib and bevacizumab. ... One consideration is that our trial used investigator assessment of response and disease progression, whereas previous randomized trials used blinded independent radiologic review,” Dr. Stinchcombe and coinvestigators summarized.

“Future studies will investigate novel osimertinib [Tagrisso] combinations and molecular markers to identify patients most likely to experience disease progression with single-agent EGFR TKIs,” they concluded.

Dr. Stinchcombe reported no relevant conflicts of interest. The trial was supported by Genentech/Roche.

SOURCE: Stinchcombe TE et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1847.

Addition of bevacizumab to erlotinib, the standard first-line therapy, failed to improve outcomes in patients with advanced epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC), according to a multicenter, phase 2, randomized, controlled trial.

“The development of erlotinib as a first-line therapy was an important advance, but there was interest in improving the efficacy of erlotinib,” noted the investigators, led by Thomas E. Stinchcombe, MD, of the Duke Cancer Institute in Durham, N.C. Preclinical data suggested that adding an antiangiogenic agent could overcome resistance, and subgroup analyses of a phase 3 trial hinted at greater efficacy of this combination in patients with EGFR-mutant disease (Lancet. 2011;377:1846-54).

The new trial was conducted among 88 patients with previously untreated stage 4 EGFR-mutant NSCLC eligible to receive bevacizumab. Two-thirds had an EGFR exon 19 deletion.

The patients were assigned evenly to receive erlotinib (Tarceva), an EGFR tyrosine kinase inhibitor, either alone or in combination with bevacizumab (Avastin), an antibody directed against vascular endothelial growth factor.

Results reported in JAMA Oncology showed that, during a median follow-up of 33 months, median progression-free survival (PFS) – the trial’s primary endpoint – was 17.9 months with the combination and 13.5 months with erlotinib alone, a nonsignificant difference (hazard ratio, 0.81; P = .39).

There was also no significant difference between groups in objective response rate (81% vs. 83%; P = .81) and overall survival (median, 32.4 vs. 50.6 months; HR, 1.41; P = .33).

Relative to the erlotinib monotherapy group, the combination therapy group had higher rates of grade 3 or worse acneiform rash (26% vs. 16%), hypertension (40% vs. 20%), and proteinuria (12% vs. 0%), but a lower rate of grade 3 or worse diarrhea (9% vs. 13%).

“Our study, unlike previous randomized clinical trials, did not reveal a significant improvement in PFS with the combination of erlotinib and bevacizumab. ... One consideration is that our trial used investigator assessment of response and disease progression, whereas previous randomized trials used blinded independent radiologic review,” Dr. Stinchcombe and coinvestigators summarized.

“Future studies will investigate novel osimertinib [Tagrisso] combinations and molecular markers to identify patients most likely to experience disease progression with single-agent EGFR TKIs,” they concluded.

Dr. Stinchcombe reported no relevant conflicts of interest. The trial was supported by Genentech/Roche.

SOURCE: Stinchcombe TE et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1847.

Addition of bevacizumab to erlotinib, the standard first-line therapy, failed to improve outcomes in patients with advanced epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC), according to a multicenter, phase 2, randomized, controlled trial.

“The development of erlotinib as a first-line therapy was an important advance, but there was interest in improving the efficacy of erlotinib,” noted the investigators, led by Thomas E. Stinchcombe, MD, of the Duke Cancer Institute in Durham, N.C. Preclinical data suggested that adding an antiangiogenic agent could overcome resistance, and subgroup analyses of a phase 3 trial hinted at greater efficacy of this combination in patients with EGFR-mutant disease (Lancet. 2011;377:1846-54).

The new trial was conducted among 88 patients with previously untreated stage 4 EGFR-mutant NSCLC eligible to receive bevacizumab. Two-thirds had an EGFR exon 19 deletion.

The patients were assigned evenly to receive erlotinib (Tarceva), an EGFR tyrosine kinase inhibitor, either alone or in combination with bevacizumab (Avastin), an antibody directed against vascular endothelial growth factor.

Results reported in JAMA Oncology showed that, during a median follow-up of 33 months, median progression-free survival (PFS) – the trial’s primary endpoint – was 17.9 months with the combination and 13.5 months with erlotinib alone, a nonsignificant difference (hazard ratio, 0.81; P = .39).

There was also no significant difference between groups in objective response rate (81% vs. 83%; P = .81) and overall survival (median, 32.4 vs. 50.6 months; HR, 1.41; P = .33).

Relative to the erlotinib monotherapy group, the combination therapy group had higher rates of grade 3 or worse acneiform rash (26% vs. 16%), hypertension (40% vs. 20%), and proteinuria (12% vs. 0%), but a lower rate of grade 3 or worse diarrhea (9% vs. 13%).

“Our study, unlike previous randomized clinical trials, did not reveal a significant improvement in PFS with the combination of erlotinib and bevacizumab. ... One consideration is that our trial used investigator assessment of response and disease progression, whereas previous randomized trials used blinded independent radiologic review,” Dr. Stinchcombe and coinvestigators summarized.

“Future studies will investigate novel osimertinib [Tagrisso] combinations and molecular markers to identify patients most likely to experience disease progression with single-agent EGFR TKIs,” they concluded.

Dr. Stinchcombe reported no relevant conflicts of interest. The trial was supported by Genentech/Roche.

SOURCE: Stinchcombe TE et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1847.

A considerable proportion of patients treated with immune checkpoint inhibitors were hospitalized for immune-related toxicities, according to a retrospective cohort study.

In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.

“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.

The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.

The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.

In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.

Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.

“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.

The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.

“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.

Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.

SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.

A considerable proportion of patients treated with immune checkpoint inhibitors were hospitalized for immune-related toxicities, according to a retrospective cohort study.

In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.

“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.

The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.

The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.

In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.

Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.

“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.

The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.

“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.

Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.

SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.

A considerable proportion of patients treated with immune checkpoint inhibitors were hospitalized for immune-related toxicities, according to a retrospective cohort study.

In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.

“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.

The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.

The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.

In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.

Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.

“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.

The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.

“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.

Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.

SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.

Single-agent therapy with either bevacizumab or pemetrexed is efficacious as maintenance therapy for patients with advanced nonsquamous non–small cell lung cancer (NSCLC), but the combination of the two agents offers no survival benefit and is more toxic, results of the randomized ECOG-ACRIN 5508 study show.

Neil Osterweil/MDedge News

For patients with no disease progression after four cycles of induction chemotherapy who were assigned to one of three maintenance therapy strategies, there were no differences in overall survival between those randomized to monotherapy with pemetrexed or bevacizumab or to a combination of the two agents, although progression-free survival (PFS) was better with the combination, reported Suresh S. Ramalingam, MD, from the Winship Cancer Institute of Emory University, Atlanta, and colleagues.

The incidence of grade 3 or greater adverse events was also significantly higher with the combination, compared with bevacizumab monotherapy.

Even in the age of immune checkpoint inhibitor therapy in the front line, “[i]t is clear that maintenance therapy will remain an integral part of the treatment approach to advanced nonsquamous NSCLC. The results of ECOG-ACRIN 5508 support the use of either pemetrexed or bevacizumab as a single agent in this setting,” the investigators wrote in the Journal of Clinical Oncology.

Although the combination of bevacizumab and pemetrexed was associated with a significant improvement in PFS in a randomized trial, the three maintenance strategies have never before been directly compared, Dr. Ramalingam and associates noted.

­In ECOG-ACRIN 5508, 1,516 patients with advanced nonsquamous NSCLC who had not received prior systemic therapy were given standard induction chemotherapy, consisting of carboplatin to an area under the curve of 6, paclitaxel 200 mg/m², and bevacizumab 15 mg/kg for up to four cycles.

Patients without progression after four cycles (874) were randomly assigned to maintenance therapy with bevacizumab at 15 mg/kg , pemetrexed 500 mg/m², or a combination of the two agents.

For the primary endpoint of overall survival, with bevacizumab serving as the control group for comparison, the investigators found that, at a median follow-up of 50.6 months, median survival was 15.9 months with pemetrexed, compared with 14.4 months with bevacizumab, a difference that was not statistically significant. Median survival with the combination was 16.4 months and was also not significantly different from bevacizumab.

Median PFS was 4.2 months and 5.1 months for the pemetrexed and bevacizumab groups, respectively, with no significant difference. In contrast, median was 7.5 months with the combination, which was significantly better than controls, with a hazard ratio of 0.67 (P less than .001).

Patients received a median of six maintenance therapy cycles for each of the single agents, and a median of eight for the combinations. The incidence of grade 3-4 toxicity was 29% with bevacizumab, 37% with pemetrexed, and 51% with the combination. The combination was associated with a significantly greater incidence of toxicities, compared with bevacizumab (P less than .001).

The study was supported by grants from the National Cancer Institute. Dr. Ramalingam reported a consulting/advisory role for bevacizumab maker Genentech/Roche and others. Multiple coauthors reported similar disclosures.

SOURCE: Ramalingam SS et al. J Clin Oncol. 2019 Jul 30. doi: 10.1200/JCO.19.01006.

Single-agent therapy with either bevacizumab or pemetrexed is efficacious as maintenance therapy for patients with advanced nonsquamous non–small cell lung cancer (NSCLC), but the combination of the two agents offers no survival benefit and is more toxic, results of the randomized ECOG-ACRIN 5508 study show.

Neil Osterweil/MDedge News

For patients with no disease progression after four cycles of induction chemotherapy who were assigned to one of three maintenance therapy strategies, there were no differences in overall survival between those randomized to monotherapy with pemetrexed or bevacizumab or to a combination of the two agents, although progression-free survival (PFS) was better with the combination, reported Suresh S. Ramalingam, MD, from the Winship Cancer Institute of Emory University, Atlanta, and colleagues.

The incidence of grade 3 or greater adverse events was also significantly higher with the combination, compared with bevacizumab monotherapy.

Even in the age of immune checkpoint inhibitor therapy in the front line, “[i]t is clear that maintenance therapy will remain an integral part of the treatment approach to advanced nonsquamous NSCLC. The results of ECOG-ACRIN 5508 support the use of either pemetrexed or bevacizumab as a single agent in this setting,” the investigators wrote in the Journal of Clinical Oncology.

Although the combination of bevacizumab and pemetrexed was associated with a significant improvement in PFS in a randomized trial, the three maintenance strategies have never before been directly compared, Dr. Ramalingam and associates noted.

­In ECOG-ACRIN 5508, 1,516 patients with advanced nonsquamous NSCLC who had not received prior systemic therapy were given standard induction chemotherapy, consisting of carboplatin to an area under the curve of 6, paclitaxel 200 mg/m², and bevacizumab 15 mg/kg for up to four cycles.

Patients without progression after four cycles (874) were randomly assigned to maintenance therapy with bevacizumab at 15 mg/kg , pemetrexed 500 mg/m², or a combination of the two agents.

For the primary endpoint of overall survival, with bevacizumab serving as the control group for comparison, the investigators found that, at a median follow-up of 50.6 months, median survival was 15.9 months with pemetrexed, compared with 14.4 months with bevacizumab, a difference that was not statistically significant. Median survival with the combination was 16.4 months and was also not significantly different from bevacizumab.

Median PFS was 4.2 months and 5.1 months for the pemetrexed and bevacizumab groups, respectively, with no significant difference. In contrast, median was 7.5 months with the combination, which was significantly better than controls, with a hazard ratio of 0.67 (P less than .001).

Patients received a median of six maintenance therapy cycles for each of the single agents, and a median of eight for the combinations. The incidence of grade 3-4 toxicity was 29% with bevacizumab, 37% with pemetrexed, and 51% with the combination. The combination was associated with a significantly greater incidence of toxicities, compared with bevacizumab (P less than .001).

The study was supported by grants from the National Cancer Institute. Dr. Ramalingam reported a consulting/advisory role for bevacizumab maker Genentech/Roche and others. Multiple coauthors reported similar disclosures.

SOURCE: Ramalingam SS et al. J Clin Oncol. 2019 Jul 30. doi: 10.1200/JCO.19.01006.

Single-agent therapy with either bevacizumab or pemetrexed is efficacious as maintenance therapy for patients with advanced nonsquamous non–small cell lung cancer (NSCLC), but the combination of the two agents offers no survival benefit and is more toxic, results of the randomized ECOG-ACRIN 5508 study show.

Neil Osterweil/MDedge News

For patients with no disease progression after four cycles of induction chemotherapy who were assigned to one of three maintenance therapy strategies, there were no differences in overall survival between those randomized to monotherapy with pemetrexed or bevacizumab or to a combination of the two agents, although progression-free survival (PFS) was better with the combination, reported Suresh S. Ramalingam, MD, from the Winship Cancer Institute of Emory University, Atlanta, and colleagues.

The incidence of grade 3 or greater adverse events was also significantly higher with the combination, compared with bevacizumab monotherapy.

Even in the age of immune checkpoint inhibitor therapy in the front line, “[i]t is clear that maintenance therapy will remain an integral part of the treatment approach to advanced nonsquamous NSCLC. The results of ECOG-ACRIN 5508 support the use of either pemetrexed or bevacizumab as a single agent in this setting,” the investigators wrote in the Journal of Clinical Oncology.

Although the combination of bevacizumab and pemetrexed was associated with a significant improvement in PFS in a randomized trial, the three maintenance strategies have never before been directly compared, Dr. Ramalingam and associates noted.

­In ECOG-ACRIN 5508, 1,516 patients with advanced nonsquamous NSCLC who had not received prior systemic therapy were given standard induction chemotherapy, consisting of carboplatin to an area under the curve of 6, paclitaxel 200 mg/m², and bevacizumab 15 mg/kg for up to four cycles.

Patients without progression after four cycles (874) were randomly assigned to maintenance therapy with bevacizumab at 15 mg/kg , pemetrexed 500 mg/m², or a combination of the two agents.

For the primary endpoint of overall survival, with bevacizumab serving as the control group for comparison, the investigators found that, at a median follow-up of 50.6 months, median survival was 15.9 months with pemetrexed, compared with 14.4 months with bevacizumab, a difference that was not statistically significant. Median survival with the combination was 16.4 months and was also not significantly different from bevacizumab.

Median PFS was 4.2 months and 5.1 months for the pemetrexed and bevacizumab groups, respectively, with no significant difference. In contrast, median was 7.5 months with the combination, which was significantly better than controls, with a hazard ratio of 0.67 (P less than .001).

Patients received a median of six maintenance therapy cycles for each of the single agents, and a median of eight for the combinations. The incidence of grade 3-4 toxicity was 29% with bevacizumab, 37% with pemetrexed, and 51% with the combination. The combination was associated with a significantly greater incidence of toxicities, compared with bevacizumab (P less than .001).

The study was supported by grants from the National Cancer Institute. Dr. Ramalingam reported a consulting/advisory role for bevacizumab maker Genentech/Roche and others. Multiple coauthors reported similar disclosures.

SOURCE: Ramalingam SS et al. J Clin Oncol. 2019 Jul 30. doi: 10.1200/JCO.19.01006.

Shared decision making around low-dose computed tomography screening for lung cancer should include risk and benefit information for baseline conditions such as chronic obstructive pulmonary disease (COPD), research suggests.

picsfive/Fotolia.com

Jonathan M. Iaccarino, MD, of the pulmonary center at the Boston University, and coauthors reported the results of a secondary analysis of patient-level outcomes from 75,138 low-dose CT (LDCT) scans in 26,453 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016).

Currently, LDCT screening is recommended annually for high-risk smokers aged 55-80 years. The National Lung Screening Trial showed that this screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in this group. The guidelines stress the importance of shared decision making, with discussion of the risks and benefits of screening.

Dr. Iaccarino and colleagues point out that decision aids for shared decision making need to include important baseline characteristics, such as the presence of COPD, as these can complicate the risk and benefit analysis.

In this study, they found that 14.2% of LDCT scans performed led to a subsequent diagnostic study and 1.5% resulted in an invasive procedure. In addition, 0.3% of scans resulted in a procedure-related complication, and in 89 cases (0.1%), this procedure-related complication was serious.

At the patient level, nearly one-third (30.5%) received a diagnostic study, 4.2% underwent an invasive procedure – 41% of whom ultimately were found not to have lung cancer – 0.9% had a procedure-related complication, and 0.3% had a serious procedure related complication. Furthermore, among those who experienced a serious complication, 12.5% were found not to have lung cancer.

“Our study analyzes cumulative outcomes at the level of the individual patient over the three years of LDCT screening during the NLST, showing higher rates of diagnostic procedures, invasive procedures, complications and serious complications than apparent when data is presented at the level of the individual test,” the authors wrote.

The 4,632 participants with COPD were significantly more likely to undergo diagnostic studies (36.2%), have an invasive procedure (6%), experience a procedure-related complication (1.5%) and experience a serious procedure-related complication (0.6%) than were participants without COPD. However, they also had a significantly higher incidence of lung cancer diagnosis than did participants without COPD (6.1% vs. 3.6%).

“While most decision aids note the risks of screening may be increased in those with COPD, our study helps quantify these increased risks as well as the increased likelihood of a lung cancer diagnosis, a critical advance given that providing personalized (rather than generic) information results in more accurate risk perception and more informed choices among individuals considering screening,” the authors wrote. “With the significant change in the balance of benefits and risks of screening in patients with COPD, it is critical to adjust the shared decision-making discussions accordingly.”

They also noted that other comorbidities, such as heart disease, vascular disease, and other lung diseases, would likely affect the balance of risk and benefit of LDCT screening, and that there was a need for further exploration of screening in these patients.

Noting the study’s limitations, the authors pointed that their analysis focused on outcomes that were not the primary outcomes of the National Lung Screening trial, and that they relied on self-reported COPD diagnoses.

The study was supported by the American Society of Clinical Oncology, the Charles A. King Trust, and Edith Nourse Rogers Memorial Veterans Hospital. No conflicts of interest were declared.

SOURCE: Iaccarino JM et al. CHEST 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016.

Shared decision making around low-dose computed tomography screening for lung cancer should include risk and benefit information for baseline conditions such as chronic obstructive pulmonary disease (COPD), research suggests.

picsfive/Fotolia.com

Jonathan M. Iaccarino, MD, of the pulmonary center at the Boston University, and coauthors reported the results of a secondary analysis of patient-level outcomes from 75,138 low-dose CT (LDCT) scans in 26,453 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016).

Currently, LDCT screening is recommended annually for high-risk smokers aged 55-80 years. The National Lung Screening Trial showed that this screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in this group. The guidelines stress the importance of shared decision making, with discussion of the risks and benefits of screening.

Dr. Iaccarino and colleagues point out that decision aids for shared decision making need to include important baseline characteristics, such as the presence of COPD, as these can complicate the risk and benefit analysis.

In this study, they found that 14.2% of LDCT scans performed led to a subsequent diagnostic study and 1.5% resulted in an invasive procedure. In addition, 0.3% of scans resulted in a procedure-related complication, and in 89 cases (0.1%), this procedure-related complication was serious.

At the patient level, nearly one-third (30.5%) received a diagnostic study, 4.2% underwent an invasive procedure – 41% of whom ultimately were found not to have lung cancer – 0.9% had a procedure-related complication, and 0.3% had a serious procedure related complication. Furthermore, among those who experienced a serious complication, 12.5% were found not to have lung cancer.

“Our study analyzes cumulative outcomes at the level of the individual patient over the three years of LDCT screening during the NLST, showing higher rates of diagnostic procedures, invasive procedures, complications and serious complications than apparent when data is presented at the level of the individual test,” the authors wrote.

The 4,632 participants with COPD were significantly more likely to undergo diagnostic studies (36.2%), have an invasive procedure (6%), experience a procedure-related complication (1.5%) and experience a serious procedure-related complication (0.6%) than were participants without COPD. However, they also had a significantly higher incidence of lung cancer diagnosis than did participants without COPD (6.1% vs. 3.6%).

“While most decision aids note the risks of screening may be increased in those with COPD, our study helps quantify these increased risks as well as the increased likelihood of a lung cancer diagnosis, a critical advance given that providing personalized (rather than generic) information results in more accurate risk perception and more informed choices among individuals considering screening,” the authors wrote. “With the significant change in the balance of benefits and risks of screening in patients with COPD, it is critical to adjust the shared decision-making discussions accordingly.”

They also noted that other comorbidities, such as heart disease, vascular disease, and other lung diseases, would likely affect the balance of risk and benefit of LDCT screening, and that there was a need for further exploration of screening in these patients.

Noting the study’s limitations, the authors pointed that their analysis focused on outcomes that were not the primary outcomes of the National Lung Screening trial, and that they relied on self-reported COPD diagnoses.

The study was supported by the American Society of Clinical Oncology, the Charles A. King Trust, and Edith Nourse Rogers Memorial Veterans Hospital. No conflicts of interest were declared.

SOURCE: Iaccarino JM et al. CHEST 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016.

Shared decision making around low-dose computed tomography screening for lung cancer should include risk and benefit information for baseline conditions such as chronic obstructive pulmonary disease (COPD), research suggests.

picsfive/Fotolia.com

Jonathan M. Iaccarino, MD, of the pulmonary center at the Boston University, and coauthors reported the results of a secondary analysis of patient-level outcomes from 75,138 low-dose CT (LDCT) scans in 26,453 participants in the National Lung Screening Trial (Chest 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016).

Currently, LDCT screening is recommended annually for high-risk smokers aged 55-80 years. The National Lung Screening Trial showed that this screening achieved a 20% relative reduction in lung cancer mortality and 6.7% relative reduction in overall mortality in this group. The guidelines stress the importance of shared decision making, with discussion of the risks and benefits of screening.

Dr. Iaccarino and colleagues point out that decision aids for shared decision making need to include important baseline characteristics, such as the presence of COPD, as these can complicate the risk and benefit analysis.

In this study, they found that 14.2% of LDCT scans performed led to a subsequent diagnostic study and 1.5% resulted in an invasive procedure. In addition, 0.3% of scans resulted in a procedure-related complication, and in 89 cases (0.1%), this procedure-related complication was serious.

At the patient level, nearly one-third (30.5%) received a diagnostic study, 4.2% underwent an invasive procedure – 41% of whom ultimately were found not to have lung cancer – 0.9% had a procedure-related complication, and 0.3% had a serious procedure related complication. Furthermore, among those who experienced a serious complication, 12.5% were found not to have lung cancer.

“Our study analyzes cumulative outcomes at the level of the individual patient over the three years of LDCT screening during the NLST, showing higher rates of diagnostic procedures, invasive procedures, complications and serious complications than apparent when data is presented at the level of the individual test,” the authors wrote.

The 4,632 participants with COPD were significantly more likely to undergo diagnostic studies (36.2%), have an invasive procedure (6%), experience a procedure-related complication (1.5%) and experience a serious procedure-related complication (0.6%) than were participants without COPD. However, they also had a significantly higher incidence of lung cancer diagnosis than did participants without COPD (6.1% vs. 3.6%).

“While most decision aids note the risks of screening may be increased in those with COPD, our study helps quantify these increased risks as well as the increased likelihood of a lung cancer diagnosis, a critical advance given that providing personalized (rather than generic) information results in more accurate risk perception and more informed choices among individuals considering screening,” the authors wrote. “With the significant change in the balance of benefits and risks of screening in patients with COPD, it is critical to adjust the shared decision-making discussions accordingly.”

They also noted that other comorbidities, such as heart disease, vascular disease, and other lung diseases, would likely affect the balance of risk and benefit of LDCT screening, and that there was a need for further exploration of screening in these patients.

Noting the study’s limitations, the authors pointed that their analysis focused on outcomes that were not the primary outcomes of the National Lung Screening trial, and that they relied on self-reported COPD diagnoses.

The study was supported by the American Society of Clinical Oncology, the Charles A. King Trust, and Edith Nourse Rogers Memorial Veterans Hospital. No conflicts of interest were declared.

SOURCE: Iaccarino JM et al. CHEST 2019 Jul 5. doi: 10.1016/j.chest.2019.06.016.

In this edition of “How I will treat my next patient,” I take a look at two phase 2 trials in stage IV non–small cell lung cancer (NSCLC) patients that appeared recently in JAMA Oncology. One summarizes a trial in stage IV NSCLC with four or fewer sites of metastasis (oligometastatic disease or OM), in which pembrolizumab is added to locally ablative therapy (LAT). The other examines whether LAT potentiates the response to immuno-oncology (I/O) in distant sites that were unexposed to LAT.

©Sergey Nivens/thinkstockphotos

I/O added to LAT in OM-NSCLC

Joshua M. Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues, published findings from a nonrandomized phase 2 trial in OM-NSCLC in which patients could receive LAT by any technique (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449). Patients could have synchronous or metachronous OM-NSCLC, any histology, and any PD-L1 tumor proportion score. Patients with more than four sites of metastatic disease that regressed to OM-NSCLC after prior therapy (i.e., “oligoremnant NSCLC”) were excluded.

They reported on 51 patients who received conventional-dose pembrolizumab for eight cycles after LAT. Patients without toxicity or progression were allowed to receive up to eight additional cycles of pembrolizumab. The median progression-free survival (PFS) was 19.1 months (95% confidence interval, 9.4-28.7 months), significantly longer than the historical comparison group (median PFS, 6.6 months; P = .005). Additionally, the 24-month overall survival (OS) was 77.5%. With respect to safety, no quality of life decrement or new safety signals were seen.
 

What this means in practice

As Dr. Bauml and colleagues suggest, there is strong theoretical rationale for believing that OM-NSCLC represents a special, potentially curable, population of stage IV NSCLC patients. Like the recently published work of Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues (J Clin Oncol. 2019 Jun 20;37[18]:1558-65), who studied LAT in comparison with consolidative/maintenance chemotherapy in a slightly different population of OM-NSCLC patients, the current trial moves clinical research forward.

Practically, this study has limitations that should temper a clinician’s enthusiasm for adopting the strategy of LAT, followed by I/O, as standard practice: small patient numbers, most with only one site of OM-NSCLC; comparison with historical controls; and no meaningful information about patient subsets who benefit from I/O and who do not. As the authors suggest, this study provides a strong rationale for a phase 3 trial with stratification for variables that could influence outcome. It does not inform clinical practice at the present time.
 

LAT added to I/O in stage IV NSCLC

We have limited ability to identify (the majority of) patients with metastatic NSCLC who will not benefit from I/O and no proven interventions to augment benefit in (the majority of) patients with low PD-L1 tumor proportion scores and/or low tumor mutation burden. However, the PEMBRO-RT study was designed to investigate whether LAT with stereotactic body radiation therapy (SBRT) could exploit the hypothesized increase in tumor antigen release and antigen presentation that could lead to better responses to I/O in untreated sites of disease among all patients with stage IV NSCLC.

As reported by Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute in Amsterdam and colleagues, the PEMBRO-RT study randomized 76 patients with stage IV NSCLC to pembro following SBRT to a single metastatic site (the experimental arm of the trial) or pembrolizumab alone. Pembrolizumab was given in a conventional dose and schedule in both arms of the trial and was administered within 7 days after SBRT on the experimental arm (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1478).

The primary outcome was the overall response rate (ORR) at 12 weeks. Among patients on the experimental versus control arms, the ORR was 36% and 18%, respectively (P = .07). This did not meet the prespecified endpoint of improving ORR from 20% to 50% at 12 weeks. Additionally, although improved on the pembro plus SBRT arm of the trial, the median PFS and OS did not meet statistical criteria for improvement over the control arm, except among the 47 patients in the PD-L1 negative subset.

What this means in practice

There are a lot of potentially relevant variables in this small, randomized phase 2 study. As the authors discuss, if there is a dose and schedule of RT that facilitates antigen release and presentation and or an ideal latent period after radiotherapy that promotes an “abscopal effect” from I/O, it is unclear whether the ideal schema was used in the PEMBRO-RT trial.

At present, if a patient with stage IV NSCLC requires LAT for clinical reasons during I/O treatment, the patient can receive it safely, but without the expectation that the LAT will augment overall benefit from I/O. Additional preclinical work will need to help guide us about a rational way to design the next trial to test the concept of supra-additive benefit from these modalities. Not only is this combination “not ready for prime time” in clinical care, but it’s not ready for the large numbers of patients in a phase 3 clinical trial.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at two phase 2 trials in stage IV non–small cell lung cancer (NSCLC) patients that appeared recently in JAMA Oncology. One summarizes a trial in stage IV NSCLC with four or fewer sites of metastasis (oligometastatic disease or OM), in which pembrolizumab is added to locally ablative therapy (LAT). The other examines whether LAT potentiates the response to immuno-oncology (I/O) in distant sites that were unexposed to LAT.

©Sergey Nivens/thinkstockphotos

I/O added to LAT in OM-NSCLC

Joshua M. Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues, published findings from a nonrandomized phase 2 trial in OM-NSCLC in which patients could receive LAT by any technique (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449). Patients could have synchronous or metachronous OM-NSCLC, any histology, and any PD-L1 tumor proportion score. Patients with more than four sites of metastatic disease that regressed to OM-NSCLC after prior therapy (i.e., “oligoremnant NSCLC”) were excluded.

They reported on 51 patients who received conventional-dose pembrolizumab for eight cycles after LAT. Patients without toxicity or progression were allowed to receive up to eight additional cycles of pembrolizumab. The median progression-free survival (PFS) was 19.1 months (95% confidence interval, 9.4-28.7 months), significantly longer than the historical comparison group (median PFS, 6.6 months; P = .005). Additionally, the 24-month overall survival (OS) was 77.5%. With respect to safety, no quality of life decrement or new safety signals were seen.
 

What this means in practice

As Dr. Bauml and colleagues suggest, there is strong theoretical rationale for believing that OM-NSCLC represents a special, potentially curable, population of stage IV NSCLC patients. Like the recently published work of Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues (J Clin Oncol. 2019 Jun 20;37[18]:1558-65), who studied LAT in comparison with consolidative/maintenance chemotherapy in a slightly different population of OM-NSCLC patients, the current trial moves clinical research forward.

Practically, this study has limitations that should temper a clinician’s enthusiasm for adopting the strategy of LAT, followed by I/O, as standard practice: small patient numbers, most with only one site of OM-NSCLC; comparison with historical controls; and no meaningful information about patient subsets who benefit from I/O and who do not. As the authors suggest, this study provides a strong rationale for a phase 3 trial with stratification for variables that could influence outcome. It does not inform clinical practice at the present time.
 

LAT added to I/O in stage IV NSCLC

We have limited ability to identify (the majority of) patients with metastatic NSCLC who will not benefit from I/O and no proven interventions to augment benefit in (the majority of) patients with low PD-L1 tumor proportion scores and/or low tumor mutation burden. However, the PEMBRO-RT study was designed to investigate whether LAT with stereotactic body radiation therapy (SBRT) could exploit the hypothesized increase in tumor antigen release and antigen presentation that could lead to better responses to I/O in untreated sites of disease among all patients with stage IV NSCLC.

As reported by Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute in Amsterdam and colleagues, the PEMBRO-RT study randomized 76 patients with stage IV NSCLC to pembro following SBRT to a single metastatic site (the experimental arm of the trial) or pembrolizumab alone. Pembrolizumab was given in a conventional dose and schedule in both arms of the trial and was administered within 7 days after SBRT on the experimental arm (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1478).

The primary outcome was the overall response rate (ORR) at 12 weeks. Among patients on the experimental versus control arms, the ORR was 36% and 18%, respectively (P = .07). This did not meet the prespecified endpoint of improving ORR from 20% to 50% at 12 weeks. Additionally, although improved on the pembro plus SBRT arm of the trial, the median PFS and OS did not meet statistical criteria for improvement over the control arm, except among the 47 patients in the PD-L1 negative subset.

What this means in practice

There are a lot of potentially relevant variables in this small, randomized phase 2 study. As the authors discuss, if there is a dose and schedule of RT that facilitates antigen release and presentation and or an ideal latent period after radiotherapy that promotes an “abscopal effect” from I/O, it is unclear whether the ideal schema was used in the PEMBRO-RT trial.

At present, if a patient with stage IV NSCLC requires LAT for clinical reasons during I/O treatment, the patient can receive it safely, but without the expectation that the LAT will augment overall benefit from I/O. Additional preclinical work will need to help guide us about a rational way to design the next trial to test the concept of supra-additive benefit from these modalities. Not only is this combination “not ready for prime time” in clinical care, but it’s not ready for the large numbers of patients in a phase 3 clinical trial.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at two phase 2 trials in stage IV non–small cell lung cancer (NSCLC) patients that appeared recently in JAMA Oncology. One summarizes a trial in stage IV NSCLC with four or fewer sites of metastasis (oligometastatic disease or OM), in which pembrolizumab is added to locally ablative therapy (LAT). The other examines whether LAT potentiates the response to immuno-oncology (I/O) in distant sites that were unexposed to LAT.

©Sergey Nivens/thinkstockphotos

I/O added to LAT in OM-NSCLC

Joshua M. Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues, published findings from a nonrandomized phase 2 trial in OM-NSCLC in which patients could receive LAT by any technique (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449). Patients could have synchronous or metachronous OM-NSCLC, any histology, and any PD-L1 tumor proportion score. Patients with more than four sites of metastatic disease that regressed to OM-NSCLC after prior therapy (i.e., “oligoremnant NSCLC”) were excluded.

They reported on 51 patients who received conventional-dose pembrolizumab for eight cycles after LAT. Patients without toxicity or progression were allowed to receive up to eight additional cycles of pembrolizumab. The median progression-free survival (PFS) was 19.1 months (95% confidence interval, 9.4-28.7 months), significantly longer than the historical comparison group (median PFS, 6.6 months; P = .005). Additionally, the 24-month overall survival (OS) was 77.5%. With respect to safety, no quality of life decrement or new safety signals were seen.
 

What this means in practice

As Dr. Bauml and colleagues suggest, there is strong theoretical rationale for believing that OM-NSCLC represents a special, potentially curable, population of stage IV NSCLC patients. Like the recently published work of Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues (J Clin Oncol. 2019 Jun 20;37[18]:1558-65), who studied LAT in comparison with consolidative/maintenance chemotherapy in a slightly different population of OM-NSCLC patients, the current trial moves clinical research forward.

Practically, this study has limitations that should temper a clinician’s enthusiasm for adopting the strategy of LAT, followed by I/O, as standard practice: small patient numbers, most with only one site of OM-NSCLC; comparison with historical controls; and no meaningful information about patient subsets who benefit from I/O and who do not. As the authors suggest, this study provides a strong rationale for a phase 3 trial with stratification for variables that could influence outcome. It does not inform clinical practice at the present time.
 

LAT added to I/O in stage IV NSCLC

We have limited ability to identify (the majority of) patients with metastatic NSCLC who will not benefit from I/O and no proven interventions to augment benefit in (the majority of) patients with low PD-L1 tumor proportion scores and/or low tumor mutation burden. However, the PEMBRO-RT study was designed to investigate whether LAT with stereotactic body radiation therapy (SBRT) could exploit the hypothesized increase in tumor antigen release and antigen presentation that could lead to better responses to I/O in untreated sites of disease among all patients with stage IV NSCLC.

As reported by Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute in Amsterdam and colleagues, the PEMBRO-RT study randomized 76 patients with stage IV NSCLC to pembro following SBRT to a single metastatic site (the experimental arm of the trial) or pembrolizumab alone. Pembrolizumab was given in a conventional dose and schedule in both arms of the trial and was administered within 7 days after SBRT on the experimental arm (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1478).

The primary outcome was the overall response rate (ORR) at 12 weeks. Among patients on the experimental versus control arms, the ORR was 36% and 18%, respectively (P = .07). This did not meet the prespecified endpoint of improving ORR from 20% to 50% at 12 weeks. Additionally, although improved on the pembro plus SBRT arm of the trial, the median PFS and OS did not meet statistical criteria for improvement over the control arm, except among the 47 patients in the PD-L1 negative subset.

What this means in practice

There are a lot of potentially relevant variables in this small, randomized phase 2 study. As the authors discuss, if there is a dose and schedule of RT that facilitates antigen release and presentation and or an ideal latent period after radiotherapy that promotes an “abscopal effect” from I/O, it is unclear whether the ideal schema was used in the PEMBRO-RT trial.

At present, if a patient with stage IV NSCLC requires LAT for clinical reasons during I/O treatment, the patient can receive it safely, but without the expectation that the LAT will augment overall benefit from I/O. Additional preclinical work will need to help guide us about a rational way to design the next trial to test the concept of supra-additive benefit from these modalities. Not only is this combination “not ready for prime time” in clinical care, but it’s not ready for the large numbers of patients in a phase 3 clinical trial.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.