Lung Cancer

Biomarker-driven targeted therapy was found feasible for heavily pretreated, metastatic non–small-cell lung cancer in a phase II trial reported online Aug. 1 in the Journal of Clinical Oncology.

The open-label multicenter umbrella study under the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, called the BATTLE-2, involved 200 patients with advanced NSCLC refractory to platinum-based chemotherapy and multiple other treatments. All patients underwent tumor tissue biopsies for biomarker and gene expression analyses.

The results of those assessments were then used to perform “adaptive randomization” in which the patients were assigned to one of four treatment arms deemed most likely to control their particular malignancy, said Vassiliki Papadimitrakopoulou, MD, professor of medicine in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, and her associates.

One group of 22 patients received 150 mg erlotinib once daily; the second group (42 patients) received 150 mg erlotinib daily plus 135 mg of the AKT inhibitor MK-2206 once weekly; the third group (75 patients) received 100 mg per week of MK-2206 plus 100 mg of the MEK inhibitor AZD6244 once daily; and the fourth group (61 patients) received 400 mg of sorafenib twice daily. A total of 186 patients were evaluable at 8 weeks, and the overall rate of disease control was 48% at that time. After a median follow-up of 20 months, the median progression-free survival was 2.0 months, median overall survival was 6.5 months, and the 1-year survival was 28%.

The primary endpoint of the study – disease control rate at 8 weeks – was not significantly different among the four treatment groups. It was 32% in group 1, 50% in group 2, 53% in group 3, and 46% in group 4. There were no complete responses and only 6 partial responses: 3 patients in group 3 and 3 patients in group 4. However, the study demonstrated “the utility of real-time biopsies for broad profiling of tumors that serve as a discovery vehicle for better target selection,” the investigators said (J Clin Oncol. 2016 Aug 1. doi:10.1200/JCO.2015.66.0084).

“We are currently pursuing alternative strategies in targeting KRAS mut+ tumors by incorporating knowledge derived from BATTLE 2,” they added.

This study was supported by Merck, Bayer Healthcare Pharmaceuticals, and the National Cancer Institute. Dr. Papadimitrakopoulou and her associates reported ties to numerous industry sources.

Biomarker-driven targeted therapy was found feasible for heavily pretreated, metastatic non–small-cell lung cancer in a phase II trial reported online Aug. 1 in the Journal of Clinical Oncology.

The open-label multicenter umbrella study under the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, called the BATTLE-2, involved 200 patients with advanced NSCLC refractory to platinum-based chemotherapy and multiple other treatments. All patients underwent tumor tissue biopsies for biomarker and gene expression analyses.

The results of those assessments were then used to perform “adaptive randomization” in which the patients were assigned to one of four treatment arms deemed most likely to control their particular malignancy, said Vassiliki Papadimitrakopoulou, MD, professor of medicine in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, and her associates.

One group of 22 patients received 150 mg erlotinib once daily; the second group (42 patients) received 150 mg erlotinib daily plus 135 mg of the AKT inhibitor MK-2206 once weekly; the third group (75 patients) received 100 mg per week of MK-2206 plus 100 mg of the MEK inhibitor AZD6244 once daily; and the fourth group (61 patients) received 400 mg of sorafenib twice daily. A total of 186 patients were evaluable at 8 weeks, and the overall rate of disease control was 48% at that time. After a median follow-up of 20 months, the median progression-free survival was 2.0 months, median overall survival was 6.5 months, and the 1-year survival was 28%.

The primary endpoint of the study – disease control rate at 8 weeks – was not significantly different among the four treatment groups. It was 32% in group 1, 50% in group 2, 53% in group 3, and 46% in group 4. There were no complete responses and only 6 partial responses: 3 patients in group 3 and 3 patients in group 4. However, the study demonstrated “the utility of real-time biopsies for broad profiling of tumors that serve as a discovery vehicle for better target selection,” the investigators said (J Clin Oncol. 2016 Aug 1. doi:10.1200/JCO.2015.66.0084).

“We are currently pursuing alternative strategies in targeting KRAS mut+ tumors by incorporating knowledge derived from BATTLE 2,” they added.

This study was supported by Merck, Bayer Healthcare Pharmaceuticals, and the National Cancer Institute. Dr. Papadimitrakopoulou and her associates reported ties to numerous industry sources.

Biomarker-driven targeted therapy was found feasible for heavily pretreated, metastatic non–small-cell lung cancer in a phase II trial reported online Aug. 1 in the Journal of Clinical Oncology.

The open-label multicenter umbrella study under the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, called the BATTLE-2, involved 200 patients with advanced NSCLC refractory to platinum-based chemotherapy and multiple other treatments. All patients underwent tumor tissue biopsies for biomarker and gene expression analyses.

The results of those assessments were then used to perform “adaptive randomization” in which the patients were assigned to one of four treatment arms deemed most likely to control their particular malignancy, said Vassiliki Papadimitrakopoulou, MD, professor of medicine in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, and her associates.

One group of 22 patients received 150 mg erlotinib once daily; the second group (42 patients) received 150 mg erlotinib daily plus 135 mg of the AKT inhibitor MK-2206 once weekly; the third group (75 patients) received 100 mg per week of MK-2206 plus 100 mg of the MEK inhibitor AZD6244 once daily; and the fourth group (61 patients) received 400 mg of sorafenib twice daily. A total of 186 patients were evaluable at 8 weeks, and the overall rate of disease control was 48% at that time. After a median follow-up of 20 months, the median progression-free survival was 2.0 months, median overall survival was 6.5 months, and the 1-year survival was 28%.

The primary endpoint of the study – disease control rate at 8 weeks – was not significantly different among the four treatment groups. It was 32% in group 1, 50% in group 2, 53% in group 3, and 46% in group 4. There were no complete responses and only 6 partial responses: 3 patients in group 3 and 3 patients in group 4. However, the study demonstrated “the utility of real-time biopsies for broad profiling of tumors that serve as a discovery vehicle for better target selection,” the investigators said (J Clin Oncol. 2016 Aug 1. doi:10.1200/JCO.2015.66.0084).

“We are currently pursuing alternative strategies in targeting KRAS mut+ tumors by incorporating knowledge derived from BATTLE 2,” they added.

This study was supported by Merck, Bayer Healthcare Pharmaceuticals, and the National Cancer Institute. Dr. Papadimitrakopoulou and her associates reported ties to numerous industry sources.

For patients with extensive-stage small-cell lung cancer, adding the anti–CTLA-4 antibody ipilimumab (Yervoy) to etoposide and platinum did not improve overall survival, compared with administering etoposide and platinum alone, investigators reported in the Journal of Clinical Oncology.

“Although exploratory in nature, chemotherapy plus ipilimumab did not demonstrate significant improvement in other endpoints, and no subgroups demonstrated greater benefit versus chemotherapy alone,” added Martin Reck, MD, of LungenClinic Grosshansdorf (Germany), and his associates.

The randomized phase III study enrolled 1,132 chemotherapy-naive patients who were randomly assigned to either chemotherapy plus ipilimumab (etoposide plus investigator’s choice of cisplatin or carboplatin during cycles one to four, and ipilimumab during cycles three to six) or to chemotherapy plus placebo (etoposide plus investigator’s choice of cisplatin or carboplatin during cycles one to four, and placebo during cycles three to six). Patients with a complete or partial response during induction could undergo prophylactic cranial irradiation before starting maintenance ipilimumab (10 mg/kg) or placebo administered every 12 weeks, the investigators reported (J Clin Oncol. 2016 July 26. doi:10.1200/JCO.2016.67.6601).

Among 954 patients who received at least one dose of study therapy, the primary endpoint, median overall survival, was 11.0 months for the ipilimumab-chemotherapy arm and 10.9 months for the placebo arm (hazard ratio, 0.9; 95% confidence interval, 0.8-1.1; P = .4). “Across most prespecified patient subgroups, hazard ratios for overall survival [also] did not seem to favor one treatment arm,” the researchers wrote.

Ipilimumab also failed to achieve a meaningful increase in median progression-free survival, compared with placebo (4.6 months and 4.4 months, respectively). There was only one complete response in the ipilimumab-chemotherapy group and none in the chemotherapy-placebo group. A total of 62% of patients achieved a partial response in each group, and the median duration of response was 4 months in the ipilimumab-chemotherapy group (95% CI, 3.3-4.2 months) versus 3.5 months (95% CI, 3.3-4.1 months) in the chemotherapy-placebo group.

There were no new or unexpected safety signals, but ipilimumab was associated with higher rates of overall and severe-grade diarrhea, colitis, and rash. The five treatment-related deaths in the ipilimumab-chemotherapy group included two from colitis, two from sepsis, and one from liver toxicity. “In the chemotherapy plus placebo arm, there were two treatment-related deaths, one resulting from sepsis and one from bone marrow suppression,” the researchers wrote. Treatment-related discontinuations also were more common with ipilimumab plus chemotherapy (18%) than with chemotherapy plus placebo (2%).

“To date, PD-1 inhibitors, alone or in combination with CTLA-4 inhibitors, show the most promise in small-cell lung cancer,” the investigators said. Multiple trials are exploring the use of these agents as maintenance therapy or in second-line settings, they added.

Bristol-Myers Squibb makes ipilimumab, funded the study, and helped collect and analyze the data. Dr. Reck disclosed financial ties to Bristol-Myers Squibb, Hoffmann-La Roche, Eli Lilly, Merck Sharp & Dohme, and several other pharmaceutical companies.

tor@frontlinemedcom.com

For patients with extensive-stage small-cell lung cancer, adding the anti–CTLA-4 antibody ipilimumab (Yervoy) to etoposide and platinum did not improve overall survival, compared with administering etoposide and platinum alone, investigators reported in the Journal of Clinical Oncology.

“Although exploratory in nature, chemotherapy plus ipilimumab did not demonstrate significant improvement in other endpoints, and no subgroups demonstrated greater benefit versus chemotherapy alone,” added Martin Reck, MD, of LungenClinic Grosshansdorf (Germany), and his associates.

The randomized phase III study enrolled 1,132 chemotherapy-naive patients who were randomly assigned to either chemotherapy plus ipilimumab (etoposide plus investigator’s choice of cisplatin or carboplatin during cycles one to four, and ipilimumab during cycles three to six) or to chemotherapy plus placebo (etoposide plus investigator’s choice of cisplatin or carboplatin during cycles one to four, and placebo during cycles three to six). Patients with a complete or partial response during induction could undergo prophylactic cranial irradiation before starting maintenance ipilimumab (10 mg/kg) or placebo administered every 12 weeks, the investigators reported (J Clin Oncol. 2016 July 26. doi:10.1200/JCO.2016.67.6601).

Among 954 patients who received at least one dose of study therapy, the primary endpoint, median overall survival, was 11.0 months for the ipilimumab-chemotherapy arm and 10.9 months for the placebo arm (hazard ratio, 0.9; 95% confidence interval, 0.8-1.1; P = .4). “Across most prespecified patient subgroups, hazard ratios for overall survival [also] did not seem to favor one treatment arm,” the researchers wrote.

Ipilimumab also failed to achieve a meaningful increase in median progression-free survival, compared with placebo (4.6 months and 4.4 months, respectively). There was only one complete response in the ipilimumab-chemotherapy group and none in the chemotherapy-placebo group. A total of 62% of patients achieved a partial response in each group, and the median duration of response was 4 months in the ipilimumab-chemotherapy group (95% CI, 3.3-4.2 months) versus 3.5 months (95% CI, 3.3-4.1 months) in the chemotherapy-placebo group.

There were no new or unexpected safety signals, but ipilimumab was associated with higher rates of overall and severe-grade diarrhea, colitis, and rash. The five treatment-related deaths in the ipilimumab-chemotherapy group included two from colitis, two from sepsis, and one from liver toxicity. “In the chemotherapy plus placebo arm, there were two treatment-related deaths, one resulting from sepsis and one from bone marrow suppression,” the researchers wrote. Treatment-related discontinuations also were more common with ipilimumab plus chemotherapy (18%) than with chemotherapy plus placebo (2%).

“To date, PD-1 inhibitors, alone or in combination with CTLA-4 inhibitors, show the most promise in small-cell lung cancer,” the investigators said. Multiple trials are exploring the use of these agents as maintenance therapy or in second-line settings, they added.

Bristol-Myers Squibb makes ipilimumab, funded the study, and helped collect and analyze the data. Dr. Reck disclosed financial ties to Bristol-Myers Squibb, Hoffmann-La Roche, Eli Lilly, Merck Sharp & Dohme, and several other pharmaceutical companies.

tor@frontlinemedcom.com

For patients with extensive-stage small-cell lung cancer, adding the anti–CTLA-4 antibody ipilimumab (Yervoy) to etoposide and platinum did not improve overall survival, compared with administering etoposide and platinum alone, investigators reported in the Journal of Clinical Oncology.

“Although exploratory in nature, chemotherapy plus ipilimumab did not demonstrate significant improvement in other endpoints, and no subgroups demonstrated greater benefit versus chemotherapy alone,” added Martin Reck, MD, of LungenClinic Grosshansdorf (Germany), and his associates.

The randomized phase III study enrolled 1,132 chemotherapy-naive patients who were randomly assigned to either chemotherapy plus ipilimumab (etoposide plus investigator’s choice of cisplatin or carboplatin during cycles one to four, and ipilimumab during cycles three to six) or to chemotherapy plus placebo (etoposide plus investigator’s choice of cisplatin or carboplatin during cycles one to four, and placebo during cycles three to six). Patients with a complete or partial response during induction could undergo prophylactic cranial irradiation before starting maintenance ipilimumab (10 mg/kg) or placebo administered every 12 weeks, the investigators reported (J Clin Oncol. 2016 July 26. doi:10.1200/JCO.2016.67.6601).

Among 954 patients who received at least one dose of study therapy, the primary endpoint, median overall survival, was 11.0 months for the ipilimumab-chemotherapy arm and 10.9 months for the placebo arm (hazard ratio, 0.9; 95% confidence interval, 0.8-1.1; P = .4). “Across most prespecified patient subgroups, hazard ratios for overall survival [also] did not seem to favor one treatment arm,” the researchers wrote.

Ipilimumab also failed to achieve a meaningful increase in median progression-free survival, compared with placebo (4.6 months and 4.4 months, respectively). There was only one complete response in the ipilimumab-chemotherapy group and none in the chemotherapy-placebo group. A total of 62% of patients achieved a partial response in each group, and the median duration of response was 4 months in the ipilimumab-chemotherapy group (95% CI, 3.3-4.2 months) versus 3.5 months (95% CI, 3.3-4.1 months) in the chemotherapy-placebo group.

There were no new or unexpected safety signals, but ipilimumab was associated with higher rates of overall and severe-grade diarrhea, colitis, and rash. The five treatment-related deaths in the ipilimumab-chemotherapy group included two from colitis, two from sepsis, and one from liver toxicity. “In the chemotherapy plus placebo arm, there were two treatment-related deaths, one resulting from sepsis and one from bone marrow suppression,” the researchers wrote. Treatment-related discontinuations also were more common with ipilimumab plus chemotherapy (18%) than with chemotherapy plus placebo (2%).

“To date, PD-1 inhibitors, alone or in combination with CTLA-4 inhibitors, show the most promise in small-cell lung cancer,” the investigators said. Multiple trials are exploring the use of these agents as maintenance therapy or in second-line settings, they added.

Bristol-Myers Squibb makes ipilimumab, funded the study, and helped collect and analyze the data. Dr. Reck disclosed financial ties to Bristol-Myers Squibb, Hoffmann-La Roche, Eli Lilly, Merck Sharp & Dohme, and several other pharmaceutical companies.

tor@frontlinemedcom.com

Ceritinib produced clinically meaningful, durable responses in patients who had advanced non–small-cell lung cancer and a history of multiple treatments with chemotherapies and crizotinib, according to investigators.

Ceritinib was effective even in patients with brain metastases, and it both reduced a high tumor burden and improved lung symptoms, said Lucio Crino, MD, of the University Medical School of Perugia (Italy) and his associates.

©Sebastian Kaulitzki/Thinkstock

They assessed ceritinib in a single-arm, open-label, phase II trial involving 140 adults with advanced ALK-rearranged non–small-cell lung cancer at 51 sites worldwide who had received at least two lines of antineoplastic chemotherapy and had progressed while taking crizotinib. A total of 100 patients (72%) had brain metastases.

After a median follow-up of 11 months (range, 0-19 months), the overall response rate was 38.6% and the disease control rate was 77.1%. Tumor burden was significantly reduced in 75.2% of patients. Treatment response was rapid, occurring at a median of 1.8 months, and durable, lasting for a median of 9.7 months. Median progression-free survival was 5.7 months, median overall survival was 14.9 months, and the 1-year overall survival rate was 63.8%.

Treatment response was similar in the subgroup of patients who had brain metastases at baseline: Their overall response rate was 33.0%, the disease control rate was 74.0%, the median duration of response was 9.2 months, and median progression-free survival was 5.4 months (J Clin Oncol. 2016 July 17. doi: 10.1200/JCO.2015.65.5936).

No new or unexpected adverse events occurred. All patients reported at least one adverse event, most commonly nausea, diarrhea, and vomiting. Most adverse events were managed without dose interruption or reduction. There was a trend toward improvement in lung symptoms such as cough, pain, and dyspnea, and both health-related quality of life and functional capacity were generally maintained throughout ceritinib treatment, Dr. Crino and his associates said.

Ceritinib produced clinically meaningful, durable responses in patients who had advanced non–small-cell lung cancer and a history of multiple treatments with chemotherapies and crizotinib, according to investigators.

Ceritinib was effective even in patients with brain metastases, and it both reduced a high tumor burden and improved lung symptoms, said Lucio Crino, MD, of the University Medical School of Perugia (Italy) and his associates.

©Sebastian Kaulitzki/Thinkstock

They assessed ceritinib in a single-arm, open-label, phase II trial involving 140 adults with advanced ALK-rearranged non–small-cell lung cancer at 51 sites worldwide who had received at least two lines of antineoplastic chemotherapy and had progressed while taking crizotinib. A total of 100 patients (72%) had brain metastases.

After a median follow-up of 11 months (range, 0-19 months), the overall response rate was 38.6% and the disease control rate was 77.1%. Tumor burden was significantly reduced in 75.2% of patients. Treatment response was rapid, occurring at a median of 1.8 months, and durable, lasting for a median of 9.7 months. Median progression-free survival was 5.7 months, median overall survival was 14.9 months, and the 1-year overall survival rate was 63.8%.

Treatment response was similar in the subgroup of patients who had brain metastases at baseline: Their overall response rate was 33.0%, the disease control rate was 74.0%, the median duration of response was 9.2 months, and median progression-free survival was 5.4 months (J Clin Oncol. 2016 July 17. doi: 10.1200/JCO.2015.65.5936).

No new or unexpected adverse events occurred. All patients reported at least one adverse event, most commonly nausea, diarrhea, and vomiting. Most adverse events were managed without dose interruption or reduction. There was a trend toward improvement in lung symptoms such as cough, pain, and dyspnea, and both health-related quality of life and functional capacity were generally maintained throughout ceritinib treatment, Dr. Crino and his associates said.

Ceritinib produced clinically meaningful, durable responses in patients who had advanced non–small-cell lung cancer and a history of multiple treatments with chemotherapies and crizotinib, according to investigators.

Ceritinib was effective even in patients with brain metastases, and it both reduced a high tumor burden and improved lung symptoms, said Lucio Crino, MD, of the University Medical School of Perugia (Italy) and his associates.

©Sebastian Kaulitzki/Thinkstock

They assessed ceritinib in a single-arm, open-label, phase II trial involving 140 adults with advanced ALK-rearranged non–small-cell lung cancer at 51 sites worldwide who had received at least two lines of antineoplastic chemotherapy and had progressed while taking crizotinib. A total of 100 patients (72%) had brain metastases.

After a median follow-up of 11 months (range, 0-19 months), the overall response rate was 38.6% and the disease control rate was 77.1%. Tumor burden was significantly reduced in 75.2% of patients. Treatment response was rapid, occurring at a median of 1.8 months, and durable, lasting for a median of 9.7 months. Median progression-free survival was 5.7 months, median overall survival was 14.9 months, and the 1-year overall survival rate was 63.8%.

Treatment response was similar in the subgroup of patients who had brain metastases at baseline: Their overall response rate was 33.0%, the disease control rate was 74.0%, the median duration of response was 9.2 months, and median progression-free survival was 5.4 months (J Clin Oncol. 2016 July 17. doi: 10.1200/JCO.2015.65.5936).

No new or unexpected adverse events occurred. All patients reported at least one adverse event, most commonly nausea, diarrhea, and vomiting. Most adverse events were managed without dose interruption or reduction. There was a trend toward improvement in lung symptoms such as cough, pain, and dyspnea, and both health-related quality of life and functional capacity were generally maintained throughout ceritinib treatment, Dr. Crino and his associates said.

The PD-1 immune checkpoint inhibitor nivolumab may be safe and effective as a first-line therapy in adult patients with non–small cell lung cancer (NSCLC), according to the results of the phase I CheckMate 012 trial.

Of 52 adult patients with advanced NSCLC who received nivolumab, 19% experienced grade three or four adverse events, and the overall response rate was 23% with four ongoing complete responses, reported Scott Gettinger, MD, of the Yale Cancer Center, New Haven, Conn., and his associates (J Clin Oncol. 2016 June. doi: 10.1200/JCO.2016.66.9929).

©Sebastian Kaulitzki/Thinkstock

In the study cohort, 94% had stage IV NSCLC, 79% were former or current smokers, and 65% had received either radiotherapy, adjuvant or neoadjuvant chemotherapy.

Treatment-related adverse events were reported in 71% of patients, the most common being fatigue (29%), rash (19%), and nausea (14%). Grade 3 or 4 adverse events including rash, cardiac failure, and lung infection occurred in 10 patients (19%). There were no treatment-related deaths, but adverse events led to the discontinuation of the drug treatment in six patients.

Responses to nivolumab (overall response rate, 23%) were durable with duration of responses ranging from 4.2 to 25.8 months. In addition, the median overall survival was 19.4 months, median progression-free survival was 3.5 months, and the 24-week progression-free survival rate was 31% (95% confidence interval, 28%-60%).

Forty-six patients had tumor specimens evaluable for PD-L1 expression. Clinical activity was observed regardless of PD-L1 expression, the investigators reported. However, the overall response rate was higher in patients with tumors that expressed PD-L1, compared with non-PD-L1-expressing tumors.

All investigators reported serving in advisory roles for, receiving financial compensation or honoraria from, or having ownership or stock in multiple companies including Bristol-Myers Squibb, which funded the study.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

The PD-1 immune checkpoint inhibitor nivolumab may be safe and effective as a first-line therapy in adult patients with non–small cell lung cancer (NSCLC), according to the results of the phase I CheckMate 012 trial.

Of 52 adult patients with advanced NSCLC who received nivolumab, 19% experienced grade three or four adverse events, and the overall response rate was 23% with four ongoing complete responses, reported Scott Gettinger, MD, of the Yale Cancer Center, New Haven, Conn., and his associates (J Clin Oncol. 2016 June. doi: 10.1200/JCO.2016.66.9929).

©Sebastian Kaulitzki/Thinkstock

In the study cohort, 94% had stage IV NSCLC, 79% were former or current smokers, and 65% had received either radiotherapy, adjuvant or neoadjuvant chemotherapy.

Treatment-related adverse events were reported in 71% of patients, the most common being fatigue (29%), rash (19%), and nausea (14%). Grade 3 or 4 adverse events including rash, cardiac failure, and lung infection occurred in 10 patients (19%). There were no treatment-related deaths, but adverse events led to the discontinuation of the drug treatment in six patients.

Responses to nivolumab (overall response rate, 23%) were durable with duration of responses ranging from 4.2 to 25.8 months. In addition, the median overall survival was 19.4 months, median progression-free survival was 3.5 months, and the 24-week progression-free survival rate was 31% (95% confidence interval, 28%-60%).

Forty-six patients had tumor specimens evaluable for PD-L1 expression. Clinical activity was observed regardless of PD-L1 expression, the investigators reported. However, the overall response rate was higher in patients with tumors that expressed PD-L1, compared with non-PD-L1-expressing tumors.

All investigators reported serving in advisory roles for, receiving financial compensation or honoraria from, or having ownership or stock in multiple companies including Bristol-Myers Squibb, which funded the study.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

The PD-1 immune checkpoint inhibitor nivolumab may be safe and effective as a first-line therapy in adult patients with non–small cell lung cancer (NSCLC), according to the results of the phase I CheckMate 012 trial.

Of 52 adult patients with advanced NSCLC who received nivolumab, 19% experienced grade three or four adverse events, and the overall response rate was 23% with four ongoing complete responses, reported Scott Gettinger, MD, of the Yale Cancer Center, New Haven, Conn., and his associates (J Clin Oncol. 2016 June. doi: 10.1200/JCO.2016.66.9929).

©Sebastian Kaulitzki/Thinkstock

In the study cohort, 94% had stage IV NSCLC, 79% were former or current smokers, and 65% had received either radiotherapy, adjuvant or neoadjuvant chemotherapy.

Treatment-related adverse events were reported in 71% of patients, the most common being fatigue (29%), rash (19%), and nausea (14%). Grade 3 or 4 adverse events including rash, cardiac failure, and lung infection occurred in 10 patients (19%). There were no treatment-related deaths, but adverse events led to the discontinuation of the drug treatment in six patients.

Responses to nivolumab (overall response rate, 23%) were durable with duration of responses ranging from 4.2 to 25.8 months. In addition, the median overall survival was 19.4 months, median progression-free survival was 3.5 months, and the 24-week progression-free survival rate was 31% (95% confidence interval, 28%-60%).

Forty-six patients had tumor specimens evaluable for PD-L1 expression. Clinical activity was observed regardless of PD-L1 expression, the investigators reported. However, the overall response rate was higher in patients with tumors that expressed PD-L1, compared with non-PD-L1-expressing tumors.

All investigators reported serving in advisory roles for, receiving financial compensation or honoraria from, or having ownership or stock in multiple companies including Bristol-Myers Squibb, which funded the study.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

In December 2015, alectinib became the third ALK inhibitor approved by the United States Food and Drug Administration for the treatment of non-small-cell lung cancer (NSCLC) that displays rearrangements of the anaplastic lymphoma kinase (ALK) gene. Alectinib is a second-generation small molecule inhibitor of the ALK protein that joins ceritinib in providing a useful treatment option for patients who have progressed on crizotinib, as a result of its ability to target crizotinib-resistant mutant forms of the ALK protein. Alectinib also displays enhanced penetrance of the blood-brain barrier, which improves efficacy against central nervous system (CNS) metastases.

Click on the PDF icon at the top of this introduction to read the full article.

In December 2015, alectinib became the third ALK inhibitor approved by the United States Food and Drug Administration for the treatment of non-small-cell lung cancer (NSCLC) that displays rearrangements of the anaplastic lymphoma kinase (ALK) gene. Alectinib is a second-generation small molecule inhibitor of the ALK protein that joins ceritinib in providing a useful treatment option for patients who have progressed on crizotinib, as a result of its ability to target crizotinib-resistant mutant forms of the ALK protein. Alectinib also displays enhanced penetrance of the blood-brain barrier, which improves efficacy against central nervous system (CNS) metastases.

Click on the PDF icon at the top of this introduction to read the full article.

In December 2015, alectinib became the third ALK inhibitor approved by the United States Food and Drug Administration for the treatment of non-small-cell lung cancer (NSCLC) that displays rearrangements of the anaplastic lymphoma kinase (ALK) gene. Alectinib is a second-generation small molecule inhibitor of the ALK protein that joins ceritinib in providing a useful treatment option for patients who have progressed on crizotinib, as a result of its ability to target crizotinib-resistant mutant forms of the ALK protein. Alectinib also displays enhanced penetrance of the blood-brain barrier, which improves efficacy against central nervous system (CNS) metastases.

Click on the PDF icon at the top of this introduction to read the full article.

BALTIMORE – Wedge resection was associated with significantly improved overall 5-year survival, compared with stereotactic body radiation therapy (SBRT) in patients with operable clinical Stage IA non–small cell lung cancer, according to a study of more than 8,000 patients.

Despite the fact that surgical resection has been the standard of care for early-stage non–small cell lung cancer (NSCLC), an increasing number of patients with potentially operable early-stage NSCLC are now being treated with SBRT, study investigator Dr. Babatunde A. Yerokun said at the annual meeting of the American Association for Thoracic Surgery.

“Our data show that thoracic surgeons should be included in the evaluation of these patients, and operative candidates with ct1A NO MO NSCLC should continue to receive a wedge resection vs. SBRT when technically feasible,” said Dr. Yerokun of Duke University, Durham, N.C. “Prospective studies are needed to determine the appropriate role of SBRT in management of these patients,” he concluded.

Dr. Yerokun and his colleagues examined overall survival of patients with cT1N0 lung cancer who underwent SBRT or wedge resection as reported in the National Cancer Data Base from 2003 to 2011. Survival was assessed using Kaplan-Meier and propensity-score matched analysis. The researchers matched groups according to common prognostic covariates, including age, sex, race, education, insurance status, facility type, and Charlson/Deyo comorbidity score, as well as tumor histology, size, and location.

Patients identified as having cT1N0 NSCLC with a tumor less than 2 cm underwent SBRT (1,514 patients) or wedge resection (6,923). Compared with the wedge resection cohort, the SBRT patients were significantly older (74 vs. 69 years) and significantly more likely to be treated at an academic comprehensive cancer program (47% vs. 37%). The median Charlson/Deyo score was lower in the SBRT patients (0 vs. 1).

In unmatched analysis, SBRT was associated with significantly lower survival than wedge resection (5-year overall survival: 32% vs. 55%). In the propensity matching, all baseline covariates, including co-morbidity scores, facility type, and tumor size, were well balanced between the SBRT and wedge groups, with 1,398 patients in each group.

However, even in the matched groups, SBRT was associated with significantly lower 5-year overall survival than wedge (33% vs. 52%). When the investigators performed a propensity matched subgroup analysis in younger patients (age less than 60 years) who had a Charlson/Deyo score of 0, SBRT was associated with worse survival with a 5-year overall survival of 59% vs. 82% for SBRT and wedge resection, respectively.

Additionally, Dr. Yerokun and his colleagues conducted a sensitivity analysis comparing centers that performed predominately wedge resection with centers that performed predominately SBRT. After the exclusion of centers with low-volume and centers that conducted either 100% wedge resection or 100% SBRT only, centers that performed predominately wedge resection were more likely to have significantly better 3-year survival.

A video of the original presentation from the AATS Annual Meeting is available online.

Dr. Yerokun reported that he had no disclosures related to this presentation.

mlesney@frontlinemedcom.com

On Twitter @ThoracicTweets

BALTIMORE – Wedge resection was associated with significantly improved overall 5-year survival, compared with stereotactic body radiation therapy (SBRT) in patients with operable clinical Stage IA non–small cell lung cancer, according to a study of more than 8,000 patients.

Despite the fact that surgical resection has been the standard of care for early-stage non–small cell lung cancer (NSCLC), an increasing number of patients with potentially operable early-stage NSCLC are now being treated with SBRT, study investigator Dr. Babatunde A. Yerokun said at the annual meeting of the American Association for Thoracic Surgery.

“Our data show that thoracic surgeons should be included in the evaluation of these patients, and operative candidates with ct1A NO MO NSCLC should continue to receive a wedge resection vs. SBRT when technically feasible,” said Dr. Yerokun of Duke University, Durham, N.C. “Prospective studies are needed to determine the appropriate role of SBRT in management of these patients,” he concluded.

Dr. Yerokun and his colleagues examined overall survival of patients with cT1N0 lung cancer who underwent SBRT or wedge resection as reported in the National Cancer Data Base from 2003 to 2011. Survival was assessed using Kaplan-Meier and propensity-score matched analysis. The researchers matched groups according to common prognostic covariates, including age, sex, race, education, insurance status, facility type, and Charlson/Deyo comorbidity score, as well as tumor histology, size, and location.

Patients identified as having cT1N0 NSCLC with a tumor less than 2 cm underwent SBRT (1,514 patients) or wedge resection (6,923). Compared with the wedge resection cohort, the SBRT patients were significantly older (74 vs. 69 years) and significantly more likely to be treated at an academic comprehensive cancer program (47% vs. 37%). The median Charlson/Deyo score was lower in the SBRT patients (0 vs. 1).

In unmatched analysis, SBRT was associated with significantly lower survival than wedge resection (5-year overall survival: 32% vs. 55%). In the propensity matching, all baseline covariates, including co-morbidity scores, facility type, and tumor size, were well balanced between the SBRT and wedge groups, with 1,398 patients in each group.

However, even in the matched groups, SBRT was associated with significantly lower 5-year overall survival than wedge (33% vs. 52%). When the investigators performed a propensity matched subgroup analysis in younger patients (age less than 60 years) who had a Charlson/Deyo score of 0, SBRT was associated with worse survival with a 5-year overall survival of 59% vs. 82% for SBRT and wedge resection, respectively.

Additionally, Dr. Yerokun and his colleagues conducted a sensitivity analysis comparing centers that performed predominately wedge resection with centers that performed predominately SBRT. After the exclusion of centers with low-volume and centers that conducted either 100% wedge resection or 100% SBRT only, centers that performed predominately wedge resection were more likely to have significantly better 3-year survival.

A video of the original presentation from the AATS Annual Meeting is available online.

Dr. Yerokun reported that he had no disclosures related to this presentation.

mlesney@frontlinemedcom.com

On Twitter @ThoracicTweets

BALTIMORE – Wedge resection was associated with significantly improved overall 5-year survival, compared with stereotactic body radiation therapy (SBRT) in patients with operable clinical Stage IA non–small cell lung cancer, according to a study of more than 8,000 patients.

Despite the fact that surgical resection has been the standard of care for early-stage non–small cell lung cancer (NSCLC), an increasing number of patients with potentially operable early-stage NSCLC are now being treated with SBRT, study investigator Dr. Babatunde A. Yerokun said at the annual meeting of the American Association for Thoracic Surgery.

“Our data show that thoracic surgeons should be included in the evaluation of these patients, and operative candidates with ct1A NO MO NSCLC should continue to receive a wedge resection vs. SBRT when technically feasible,” said Dr. Yerokun of Duke University, Durham, N.C. “Prospective studies are needed to determine the appropriate role of SBRT in management of these patients,” he concluded.

Dr. Yerokun and his colleagues examined overall survival of patients with cT1N0 lung cancer who underwent SBRT or wedge resection as reported in the National Cancer Data Base from 2003 to 2011. Survival was assessed using Kaplan-Meier and propensity-score matched analysis. The researchers matched groups according to common prognostic covariates, including age, sex, race, education, insurance status, facility type, and Charlson/Deyo comorbidity score, as well as tumor histology, size, and location.

Patients identified as having cT1N0 NSCLC with a tumor less than 2 cm underwent SBRT (1,514 patients) or wedge resection (6,923). Compared with the wedge resection cohort, the SBRT patients were significantly older (74 vs. 69 years) and significantly more likely to be treated at an academic comprehensive cancer program (47% vs. 37%). The median Charlson/Deyo score was lower in the SBRT patients (0 vs. 1).

In unmatched analysis, SBRT was associated with significantly lower survival than wedge resection (5-year overall survival: 32% vs. 55%). In the propensity matching, all baseline covariates, including co-morbidity scores, facility type, and tumor size, were well balanced between the SBRT and wedge groups, with 1,398 patients in each group.

However, even in the matched groups, SBRT was associated with significantly lower 5-year overall survival than wedge (33% vs. 52%). When the investigators performed a propensity matched subgroup analysis in younger patients (age less than 60 years) who had a Charlson/Deyo score of 0, SBRT was associated with worse survival with a 5-year overall survival of 59% vs. 82% for SBRT and wedge resection, respectively.

Additionally, Dr. Yerokun and his colleagues conducted a sensitivity analysis comparing centers that performed predominately wedge resection with centers that performed predominately SBRT. After the exclusion of centers with low-volume and centers that conducted either 100% wedge resection or 100% SBRT only, centers that performed predominately wedge resection were more likely to have significantly better 3-year survival.

A video of the original presentation from the AATS Annual Meeting is available online.

Dr. Yerokun reported that he had no disclosures related to this presentation.

mlesney@frontlinemedcom.com

On Twitter @ThoracicTweets

CHICAGO – Overall response rates ranged from 48% to 71% when pembrolizumab was added to chemotherapy combinations in patients with advanced non–small cell lung cancer (NSCLC), and close to 30% when added to an R2 inhibitor in patients with advanced NSCLC and other tumor types, according to two early phase clinical trials presented at the annual meeting of the American Society of Clinical Oncology.

Safety and efficacy of pembrolizumab in combination with either carboplatin and paclitaxel; carboplatin, paclitaxel, and bevacizumab; or carboplatin and pemetrexed were evaluated in the KEYNOTE-021 trial. Patients were split between two doses of pembrolizumab: 2 or 10 mg/kg every 3 weeks. The overall response rate for the entire cohort of 74 patients with advanced NSCLC was 57% (95% confidence interval, 45-68), reported Dr. Shirish Gadgeel of Karmanos Cancer Institute, Detroit.

For the 25 patients who received pembrolizumab, carboplatin, and paclitaxel (cohort A) the overall response was 52% (95% CI, 31-72). For the 25 patients who also received bevacizumab in addition to pembrolizumab, carboplatin, and paclitaxel (cohort B), the overall response rate was 48% (95% CI, 28-69).

Among 24 patients who received pemetrexed with pembrolizumab and carboplatin (cohort C), the overall response was the highest at 71% (95% CI, 49-87).

Grade 3 or 4 adverse events occurred in 36%, 46%, and 42% of patients in cohort A, B, and C, respectively. The most common adverse events were anemia and neutropenia including febrile neutropenia.

“Pembro in combination with standard chemotherapy regimens is feasible and yields substantial clinical efficacy regardless of pembro dose or PD-L1 status in treatment-naïve advanced NSCLC,” Dr Gadgeel said.

A randomized phase III study evaluating pemetrexed/platinum with or without pembrolizumab is currently recruiting, he said.

These combinations, while perhaps better than chemotherapy alone, may be no better than just immunotherapy alone, session moderator Dr. Scott Antonia of the Moffitt Cancer Center, Tampa, Fla., commented. “And the truth is that concurrent therapy is clearly more toxic.”

In another study presented at the meeting, led by Dr. Roy Herbst of Yale Cancer Center, New Haven, Conn., pembrolizumab was combined with ramucirumab, a recently approved vascular endothelial growth factor receptor–2 inhibitor. “Hallmarks of tumor growth include angiogenesis and immunosuppression,” Dr. Herbst and his coauthors wrote in their abstract, noting that this was the first study to combine these agents to target both processes simultaneously.

“The idea is the R2 inhibitor might have an effect on the microimmune environment and drive T cells into the tumor,” Dr. Herbst said.

The study cohort included patients with advanced gastric or gastroesophageal junction adenocarcinoma, NSCLC, and urothelial carcinoma.

Overall, the response rate was close to 30% in the first 10 patients, Dr. Herbst reported. Furthermore, the preliminary data did not reveal any unexpected safety signals.

Although the data was from a small, ongoing phase I trial, Dr. Herbst noted the data is promising. Researchers are continuing to collect data on the safety profile of this drug combination, and are planning to enroll patients with additional tumor types.

The KEYNOTE-021 trial was funded by Merck Sharp and Dohme. Dr. Gadgeel reported having a consulting or advisory role and receiving research funding from multiple companies. The trial headed by Dr. Herbst was funded by Eli Lilly. Dr. Herbst reported having a consulting or advisory role and receiving honoraria and research funding from multiple companies including Eli Lilly.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

CHICAGO – Overall response rates ranged from 48% to 71% when pembrolizumab was added to chemotherapy combinations in patients with advanced non–small cell lung cancer (NSCLC), and close to 30% when added to an R2 inhibitor in patients with advanced NSCLC and other tumor types, according to two early phase clinical trials presented at the annual meeting of the American Society of Clinical Oncology.

Safety and efficacy of pembrolizumab in combination with either carboplatin and paclitaxel; carboplatin, paclitaxel, and bevacizumab; or carboplatin and pemetrexed were evaluated in the KEYNOTE-021 trial. Patients were split between two doses of pembrolizumab: 2 or 10 mg/kg every 3 weeks. The overall response rate for the entire cohort of 74 patients with advanced NSCLC was 57% (95% confidence interval, 45-68), reported Dr. Shirish Gadgeel of Karmanos Cancer Institute, Detroit.

For the 25 patients who received pembrolizumab, carboplatin, and paclitaxel (cohort A) the overall response was 52% (95% CI, 31-72). For the 25 patients who also received bevacizumab in addition to pembrolizumab, carboplatin, and paclitaxel (cohort B), the overall response rate was 48% (95% CI, 28-69).

Among 24 patients who received pemetrexed with pembrolizumab and carboplatin (cohort C), the overall response was the highest at 71% (95% CI, 49-87).

Grade 3 or 4 adverse events occurred in 36%, 46%, and 42% of patients in cohort A, B, and C, respectively. The most common adverse events were anemia and neutropenia including febrile neutropenia.

“Pembro in combination with standard chemotherapy regimens is feasible and yields substantial clinical efficacy regardless of pembro dose or PD-L1 status in treatment-naïve advanced NSCLC,” Dr Gadgeel said.

A randomized phase III study evaluating pemetrexed/platinum with or without pembrolizumab is currently recruiting, he said.

These combinations, while perhaps better than chemotherapy alone, may be no better than just immunotherapy alone, session moderator Dr. Scott Antonia of the Moffitt Cancer Center, Tampa, Fla., commented. “And the truth is that concurrent therapy is clearly more toxic.”

In another study presented at the meeting, led by Dr. Roy Herbst of Yale Cancer Center, New Haven, Conn., pembrolizumab was combined with ramucirumab, a recently approved vascular endothelial growth factor receptor–2 inhibitor. “Hallmarks of tumor growth include angiogenesis and immunosuppression,” Dr. Herbst and his coauthors wrote in their abstract, noting that this was the first study to combine these agents to target both processes simultaneously.

“The idea is the R2 inhibitor might have an effect on the microimmune environment and drive T cells into the tumor,” Dr. Herbst said.

The study cohort included patients with advanced gastric or gastroesophageal junction adenocarcinoma, NSCLC, and urothelial carcinoma.

Overall, the response rate was close to 30% in the first 10 patients, Dr. Herbst reported. Furthermore, the preliminary data did not reveal any unexpected safety signals.

Although the data was from a small, ongoing phase I trial, Dr. Herbst noted the data is promising. Researchers are continuing to collect data on the safety profile of this drug combination, and are planning to enroll patients with additional tumor types.

The KEYNOTE-021 trial was funded by Merck Sharp and Dohme. Dr. Gadgeel reported having a consulting or advisory role and receiving research funding from multiple companies. The trial headed by Dr. Herbst was funded by Eli Lilly. Dr. Herbst reported having a consulting or advisory role and receiving honoraria and research funding from multiple companies including Eli Lilly.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

CHICAGO – Overall response rates ranged from 48% to 71% when pembrolizumab was added to chemotherapy combinations in patients with advanced non–small cell lung cancer (NSCLC), and close to 30% when added to an R2 inhibitor in patients with advanced NSCLC and other tumor types, according to two early phase clinical trials presented at the annual meeting of the American Society of Clinical Oncology.

Safety and efficacy of pembrolizumab in combination with either carboplatin and paclitaxel; carboplatin, paclitaxel, and bevacizumab; or carboplatin and pemetrexed were evaluated in the KEYNOTE-021 trial. Patients were split between two doses of pembrolizumab: 2 or 10 mg/kg every 3 weeks. The overall response rate for the entire cohort of 74 patients with advanced NSCLC was 57% (95% confidence interval, 45-68), reported Dr. Shirish Gadgeel of Karmanos Cancer Institute, Detroit.

For the 25 patients who received pembrolizumab, carboplatin, and paclitaxel (cohort A) the overall response was 52% (95% CI, 31-72). For the 25 patients who also received bevacizumab in addition to pembrolizumab, carboplatin, and paclitaxel (cohort B), the overall response rate was 48% (95% CI, 28-69).

Among 24 patients who received pemetrexed with pembrolizumab and carboplatin (cohort C), the overall response was the highest at 71% (95% CI, 49-87).

Grade 3 or 4 adverse events occurred in 36%, 46%, and 42% of patients in cohort A, B, and C, respectively. The most common adverse events were anemia and neutropenia including febrile neutropenia.

“Pembro in combination with standard chemotherapy regimens is feasible and yields substantial clinical efficacy regardless of pembro dose or PD-L1 status in treatment-naïve advanced NSCLC,” Dr Gadgeel said.

A randomized phase III study evaluating pemetrexed/platinum with or without pembrolizumab is currently recruiting, he said.

These combinations, while perhaps better than chemotherapy alone, may be no better than just immunotherapy alone, session moderator Dr. Scott Antonia of the Moffitt Cancer Center, Tampa, Fla., commented. “And the truth is that concurrent therapy is clearly more toxic.”

In another study presented at the meeting, led by Dr. Roy Herbst of Yale Cancer Center, New Haven, Conn., pembrolizumab was combined with ramucirumab, a recently approved vascular endothelial growth factor receptor–2 inhibitor. “Hallmarks of tumor growth include angiogenesis and immunosuppression,” Dr. Herbst and his coauthors wrote in their abstract, noting that this was the first study to combine these agents to target both processes simultaneously.

“The idea is the R2 inhibitor might have an effect on the microimmune environment and drive T cells into the tumor,” Dr. Herbst said.

The study cohort included patients with advanced gastric or gastroesophageal junction adenocarcinoma, NSCLC, and urothelial carcinoma.

Overall, the response rate was close to 30% in the first 10 patients, Dr. Herbst reported. Furthermore, the preliminary data did not reveal any unexpected safety signals.

Although the data was from a small, ongoing phase I trial, Dr. Herbst noted the data is promising. Researchers are continuing to collect data on the safety profile of this drug combination, and are planning to enroll patients with additional tumor types.

The KEYNOTE-021 trial was funded by Merck Sharp and Dohme. Dr. Gadgeel reported having a consulting or advisory role and receiving research funding from multiple companies. The trial headed by Dr. Herbst was funded by Eli Lilly. Dr. Herbst reported having a consulting or advisory role and receiving honoraria and research funding from multiple companies including Eli Lilly.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

The International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee has developed proposals for revision of the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published in late 2016. The new classification will be enacted in January 2017.

The changes proposed were based on the results of an analysis of a new database of 94,708 cases donated from 35 sources in 16 countries around the world.

The methods used and the proposals made were published in the Journal of Thoracic Oncology (2016;11:39-51).

Candidate proposals for the TNM stage groups were developed in conjunction with proposed changes to the T and M categories, which were previously published (J Thorac Oncol 2015;10:990-1003, and 2015;10:1515-22). There were no proposed changes to the N.

Changes to some T and M descriptors will result in these cases being assigned to a different stage than that to which they would have been assigned in the 7th edition. In addition, some TNM subsets have been moved to a new stage grouping, according to Dr. Peter Goldstraw of Imperial College, London, and his colleagues on behalf of the IASLC Staging and Prognostic Factors Committee.

Major new proposals

T1 changes: Size cut points have further proliferated in the proposals for the 8th edition, and outgrowth of the emphasis on tumor size in the 7th edition, such that size will now be a descriptor in all T categories, according to the authors. New stage groupings proposed divide stage T1 into T1a, T1b, and T1c, based on the new size cut points of 1 cm and 2 cm. This results in these cases (when associated with the categories N0 and M0) being assigned to stages 1A1, 1A2, and 1A3, respectively, which reflects the statistically different prognosis of these cases.

T3, T4 changes: A new group has been created for the most advanced local disease categories, T3 and T4 associated with N3 disease, but category M0. Such cases will now be classified as stage IIIC, reflecting their worse outcomes than seen in cases involving tumors that remain in stage IIIB. The prognosis for stage IIIC cases is similar to that of stage IVA cases, however the researchers justified the separation, based upon the different treatment approaches used for such cases.

M changes: Although cases with intrathoracic metastatic disease to the contralateral lung or with pleural/pericardial dissemination remain classified as M1a disease, the category M1b will now be assigned to cases with a single metastatic deposit (in one organ) and M1a and M1b cases will be moored to a new stage grouping called IVA. The more common situation of multiple metastatic deposits, usually in more than one organ, will be classified as M1c and staged as IVB. Separation of the M1a and M1b categories was maintained both for further data analysis and because some patients with oligometastatic disease are now receiving more aggressive local therapy in addition to systemic treatment, according to the authors.

Other proposals

A variety of more minor changes to stage groupings has also been proposed, some of which will result in a T descriptor being allocated to a higher stage. In some cases, tumors may be allocated to a different T category entirely, leading to a reclassification of stage. Among the examples given were tumors associated with diaphragmatic invasion to TV, which, when associated with N0 disease, will move from stage IIB to IIA.

Impact on treatment

The relationship of the proposed classification changes to treatment decisions is not direct, the authors stated in their discussion. “Although such changes might raise the issue of whether consequent changes to treatment algorithms are needed, it is important to remind ourselves that stage does not dictate treatment. Stage is one, and perhaps the most important, of several prognostic factors that guide the appropriate treatment option[s] to offer the patient. Any change to established treatment algorithms should be based on clinical judgment informed by prospective trials,” they emphasized.

New stage groupings should be used in any trials of novel therapies, they added.

“We hope that the thoracic oncology community finds the proposals of value and that, when accepted, will have a positive impact on the effectiveness of treatment for lung cancer, which will benefit patients around the globe,” the researchers concluded.

The research to develop the new proposals was funded by the IASLC, including funds obtained through unrestricted grants obtained from the pharmaceutical industry. The authors reported no other disclosures.

mlesney@frontlinemedcom.com

The International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee has developed proposals for revision of the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published in late 2016. The new classification will be enacted in January 2017.

The changes proposed were based on the results of an analysis of a new database of 94,708 cases donated from 35 sources in 16 countries around the world.

The methods used and the proposals made were published in the Journal of Thoracic Oncology (2016;11:39-51).

Candidate proposals for the TNM stage groups were developed in conjunction with proposed changes to the T and M categories, which were previously published (J Thorac Oncol 2015;10:990-1003, and 2015;10:1515-22). There were no proposed changes to the N.

Changes to some T and M descriptors will result in these cases being assigned to a different stage than that to which they would have been assigned in the 7th edition. In addition, some TNM subsets have been moved to a new stage grouping, according to Dr. Peter Goldstraw of Imperial College, London, and his colleagues on behalf of the IASLC Staging and Prognostic Factors Committee.

Major new proposals

T1 changes: Size cut points have further proliferated in the proposals for the 8th edition, and outgrowth of the emphasis on tumor size in the 7th edition, such that size will now be a descriptor in all T categories, according to the authors. New stage groupings proposed divide stage T1 into T1a, T1b, and T1c, based on the new size cut points of 1 cm and 2 cm. This results in these cases (when associated with the categories N0 and M0) being assigned to stages 1A1, 1A2, and 1A3, respectively, which reflects the statistically different prognosis of these cases.

T3, T4 changes: A new group has been created for the most advanced local disease categories, T3 and T4 associated with N3 disease, but category M0. Such cases will now be classified as stage IIIC, reflecting their worse outcomes than seen in cases involving tumors that remain in stage IIIB. The prognosis for stage IIIC cases is similar to that of stage IVA cases, however the researchers justified the separation, based upon the different treatment approaches used for such cases.

M changes: Although cases with intrathoracic metastatic disease to the contralateral lung or with pleural/pericardial dissemination remain classified as M1a disease, the category M1b will now be assigned to cases with a single metastatic deposit (in one organ) and M1a and M1b cases will be moored to a new stage grouping called IVA. The more common situation of multiple metastatic deposits, usually in more than one organ, will be classified as M1c and staged as IVB. Separation of the M1a and M1b categories was maintained both for further data analysis and because some patients with oligometastatic disease are now receiving more aggressive local therapy in addition to systemic treatment, according to the authors.

Other proposals

A variety of more minor changes to stage groupings has also been proposed, some of which will result in a T descriptor being allocated to a higher stage. In some cases, tumors may be allocated to a different T category entirely, leading to a reclassification of stage. Among the examples given were tumors associated with diaphragmatic invasion to TV, which, when associated with N0 disease, will move from stage IIB to IIA.

Impact on treatment

The relationship of the proposed classification changes to treatment decisions is not direct, the authors stated in their discussion. “Although such changes might raise the issue of whether consequent changes to treatment algorithms are needed, it is important to remind ourselves that stage does not dictate treatment. Stage is one, and perhaps the most important, of several prognostic factors that guide the appropriate treatment option[s] to offer the patient. Any change to established treatment algorithms should be based on clinical judgment informed by prospective trials,” they emphasized.

New stage groupings should be used in any trials of novel therapies, they added.

“We hope that the thoracic oncology community finds the proposals of value and that, when accepted, will have a positive impact on the effectiveness of treatment for lung cancer, which will benefit patients around the globe,” the researchers concluded.

The research to develop the new proposals was funded by the IASLC, including funds obtained through unrestricted grants obtained from the pharmaceutical industry. The authors reported no other disclosures.

mlesney@frontlinemedcom.com

The International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee has developed proposals for revision of the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published in late 2016. The new classification will be enacted in January 2017.

The changes proposed were based on the results of an analysis of a new database of 94,708 cases donated from 35 sources in 16 countries around the world.

The methods used and the proposals made were published in the Journal of Thoracic Oncology (2016;11:39-51).

Candidate proposals for the TNM stage groups were developed in conjunction with proposed changes to the T and M categories, which were previously published (J Thorac Oncol 2015;10:990-1003, and 2015;10:1515-22). There were no proposed changes to the N.

Changes to some T and M descriptors will result in these cases being assigned to a different stage than that to which they would have been assigned in the 7th edition. In addition, some TNM subsets have been moved to a new stage grouping, according to Dr. Peter Goldstraw of Imperial College, London, and his colleagues on behalf of the IASLC Staging and Prognostic Factors Committee.

Major new proposals

T1 changes: Size cut points have further proliferated in the proposals for the 8th edition, and outgrowth of the emphasis on tumor size in the 7th edition, such that size will now be a descriptor in all T categories, according to the authors. New stage groupings proposed divide stage T1 into T1a, T1b, and T1c, based on the new size cut points of 1 cm and 2 cm. This results in these cases (when associated with the categories N0 and M0) being assigned to stages 1A1, 1A2, and 1A3, respectively, which reflects the statistically different prognosis of these cases.

T3, T4 changes: A new group has been created for the most advanced local disease categories, T3 and T4 associated with N3 disease, but category M0. Such cases will now be classified as stage IIIC, reflecting their worse outcomes than seen in cases involving tumors that remain in stage IIIB. The prognosis for stage IIIC cases is similar to that of stage IVA cases, however the researchers justified the separation, based upon the different treatment approaches used for such cases.

M changes: Although cases with intrathoracic metastatic disease to the contralateral lung or with pleural/pericardial dissemination remain classified as M1a disease, the category M1b will now be assigned to cases with a single metastatic deposit (in one organ) and M1a and M1b cases will be moored to a new stage grouping called IVA. The more common situation of multiple metastatic deposits, usually in more than one organ, will be classified as M1c and staged as IVB. Separation of the M1a and M1b categories was maintained both for further data analysis and because some patients with oligometastatic disease are now receiving more aggressive local therapy in addition to systemic treatment, according to the authors.

Other proposals

A variety of more minor changes to stage groupings has also been proposed, some of which will result in a T descriptor being allocated to a higher stage. In some cases, tumors may be allocated to a different T category entirely, leading to a reclassification of stage. Among the examples given were tumors associated with diaphragmatic invasion to TV, which, when associated with N0 disease, will move from stage IIB to IIA.

Impact on treatment

The relationship of the proposed classification changes to treatment decisions is not direct, the authors stated in their discussion. “Although such changes might raise the issue of whether consequent changes to treatment algorithms are needed, it is important to remind ourselves that stage does not dictate treatment. Stage is one, and perhaps the most important, of several prognostic factors that guide the appropriate treatment option[s] to offer the patient. Any change to established treatment algorithms should be based on clinical judgment informed by prospective trials,” they emphasized.

New stage groupings should be used in any trials of novel therapies, they added.

“We hope that the thoracic oncology community finds the proposals of value and that, when accepted, will have a positive impact on the effectiveness of treatment for lung cancer, which will benefit patients around the globe,” the researchers concluded.

The research to develop the new proposals was funded by the IASLC, including funds obtained through unrestricted grants obtained from the pharmaceutical industry. The authors reported no other disclosures.

mlesney@frontlinemedcom.com