Lung Cancer

Key clinical point: Lorlatinib extends progression-free survival (PFS) and reduces central nervous system (CNS) progression compared with crizotinib in patients with anaplastic lymphoma kinase positive (ALK+) advanced nonsmall cell lung cancer (NSCLC) and with or without brain metastases at baseline.

Major finding: In patients with and without baseline brain metastasis, lorlatinib vs. crizotinib improved the 12-month PFS (78% vs. 22% and 78% vs. 45%, respectively) and 12-month cumulative incidence of CNS progression (7% vs. 72% and 1% vs. 18%, respectively).

Study details: The data come from a post hoc analysis of the CROWN trial including patients with ALK+ NSCLC and with (n = 78) or without (n = 218) brain metastasis at baseline.

Disclosures: The CROWN trial was funded by Pfizer. Many authors reported ties with multiple pharmaceutical companies, including Pfizer.

Source: Solomon BJ et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non–small-cell lung cancer from the phase III CROWN study. J Clin Oncol. 2022 (May 23). Doi:  10.1200/JCO.21.02278

Key clinical point: Lorlatinib extends progression-free survival (PFS) and reduces central nervous system (CNS) progression compared with crizotinib in patients with anaplastic lymphoma kinase positive (ALK+) advanced nonsmall cell lung cancer (NSCLC) and with or without brain metastases at baseline.

Major finding: In patients with and without baseline brain metastasis, lorlatinib vs. crizotinib improved the 12-month PFS (78% vs. 22% and 78% vs. 45%, respectively) and 12-month cumulative incidence of CNS progression (7% vs. 72% and 1% vs. 18%, respectively).

Study details: The data come from a post hoc analysis of the CROWN trial including patients with ALK+ NSCLC and with (n = 78) or without (n = 218) brain metastasis at baseline.

Disclosures: The CROWN trial was funded by Pfizer. Many authors reported ties with multiple pharmaceutical companies, including Pfizer.

Source: Solomon BJ et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non–small-cell lung cancer from the phase III CROWN study. J Clin Oncol. 2022 (May 23). Doi:  10.1200/JCO.21.02278

Key clinical point: Lorlatinib extends progression-free survival (PFS) and reduces central nervous system (CNS) progression compared with crizotinib in patients with anaplastic lymphoma kinase positive (ALK+) advanced nonsmall cell lung cancer (NSCLC) and with or without brain metastases at baseline.

Major finding: In patients with and without baseline brain metastasis, lorlatinib vs. crizotinib improved the 12-month PFS (78% vs. 22% and 78% vs. 45%, respectively) and 12-month cumulative incidence of CNS progression (7% vs. 72% and 1% vs. 18%, respectively).

Study details: The data come from a post hoc analysis of the CROWN trial including patients with ALK+ NSCLC and with (n = 78) or without (n = 218) brain metastasis at baseline.

Disclosures: The CROWN trial was funded by Pfizer. Many authors reported ties with multiple pharmaceutical companies, including Pfizer.

Source: Solomon BJ et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non–small-cell lung cancer from the phase III CROWN study. J Clin Oncol. 2022 (May 23). Doi:  10.1200/JCO.21.02278

Key clinical point: Ever-smokers treated with the first-line pembrolizumab for advanced nonsmall cell lung cancer (NSCLC) have a significantly longer overall survival (OS) compared with never-smokers.

Major finding: Ever-smokers vs. never-smokers treated with the first-line pembrolizumab for advanced NSCLC had a 31% longer median OS (12.8 vs. 6.5 months; hazard ratio 0.69; 95% CI 0.50-0.95) after adjusting for covariates.

Study details: The data come from a real-world retrospective cohort study of 1166 patients with advanced NSCLC (91 never-smokers and 1075 current or former smokers [ever-smokers]) treated with the first-line pembrolizumab in the U.S.

Disclosures: No funding source was identified. The authors reported ties with one or more pharmaceutical companies or research organizations.

Source: Popat S et al. Association between smoking history and overall survival in patients receiving pembrolizumab for first-line treatment of advanced non–small cell lung cancer. JAMA Netw Open. 2022;5(5):e2214046 (May 25). Doi: 10.1001/jamanetworkopen.2022.14046

Key clinical point: Ever-smokers treated with the first-line pembrolizumab for advanced nonsmall cell lung cancer (NSCLC) have a significantly longer overall survival (OS) compared with never-smokers.

Major finding: Ever-smokers vs. never-smokers treated with the first-line pembrolizumab for advanced NSCLC had a 31% longer median OS (12.8 vs. 6.5 months; hazard ratio 0.69; 95% CI 0.50-0.95) after adjusting for covariates.

Study details: The data come from a real-world retrospective cohort study of 1166 patients with advanced NSCLC (91 never-smokers and 1075 current or former smokers [ever-smokers]) treated with the first-line pembrolizumab in the U.S.

Disclosures: No funding source was identified. The authors reported ties with one or more pharmaceutical companies or research organizations.

Source: Popat S et al. Association between smoking history and overall survival in patients receiving pembrolizumab for first-line treatment of advanced non–small cell lung cancer. JAMA Netw Open. 2022;5(5):e2214046 (May 25). Doi: 10.1001/jamanetworkopen.2022.14046

Key clinical point: Ever-smokers treated with the first-line pembrolizumab for advanced nonsmall cell lung cancer (NSCLC) have a significantly longer overall survival (OS) compared with never-smokers.

Major finding: Ever-smokers vs. never-smokers treated with the first-line pembrolizumab for advanced NSCLC had a 31% longer median OS (12.8 vs. 6.5 months; hazard ratio 0.69; 95% CI 0.50-0.95) after adjusting for covariates.

Study details: The data come from a real-world retrospective cohort study of 1166 patients with advanced NSCLC (91 never-smokers and 1075 current or former smokers [ever-smokers]) treated with the first-line pembrolizumab in the U.S.

Disclosures: No funding source was identified. The authors reported ties with one or more pharmaceutical companies or research organizations.

Source: Popat S et al. Association between smoking history and overall survival in patients receiving pembrolizumab for first-line treatment of advanced non–small cell lung cancer. JAMA Netw Open. 2022;5(5):e2214046 (May 25). Doi: 10.1001/jamanetworkopen.2022.14046

Key clinical point: Lorlatinib extends progression-free survival (PFS) and reduces central nervous system (CNS) progression compared with crizotinib in patients with anaplastic lymphoma kinase positive (ALK+) advanced nonsmall cell lung cancer (NSCLC) and with or without brain metastases at baseline.

Major finding: In patients with and without baseline brain metastasis, lorlatinib vs. crizotinib improved the 12-month PFS (78% vs. 22% and 78% vs. 45%, respectively) and 12-month cumulative incidence of CNS progression (7% vs. 72% and 1% vs. 18%, respectively).

Study details: The data come from a post hoc analysis of the CROWN trial including patients with ALK+ NSCLC and with (n = 78) or without (n = 218) brain metastasis at baseline.

Disclosures: The CROWN trial was funded by Pfizer. Many authors reported ties with multiple pharmaceutical companies, including Pfizer.

Source: Solomon BJ et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non–small-cell lung cancer from the phase III CROWN study. J Clin Oncol. 2022 (May 23). Doi:  10.1200/JCO.21.02278

Key clinical point: Lorlatinib extends progression-free survival (PFS) and reduces central nervous system (CNS) progression compared with crizotinib in patients with anaplastic lymphoma kinase positive (ALK+) advanced nonsmall cell lung cancer (NSCLC) and with or without brain metastases at baseline.

Major finding: In patients with and without baseline brain metastasis, lorlatinib vs. crizotinib improved the 12-month PFS (78% vs. 22% and 78% vs. 45%, respectively) and 12-month cumulative incidence of CNS progression (7% vs. 72% and 1% vs. 18%, respectively).

Study details: The data come from a post hoc analysis of the CROWN trial including patients with ALK+ NSCLC and with (n = 78) or without (n = 218) brain metastasis at baseline.

Disclosures: The CROWN trial was funded by Pfizer. Many authors reported ties with multiple pharmaceutical companies, including Pfizer.

Source: Solomon BJ et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non–small-cell lung cancer from the phase III CROWN study. J Clin Oncol. 2022 (May 23). Doi:  10.1200/JCO.21.02278

Key clinical point: Lorlatinib extends progression-free survival (PFS) and reduces central nervous system (CNS) progression compared with crizotinib in patients with anaplastic lymphoma kinase positive (ALK+) advanced nonsmall cell lung cancer (NSCLC) and with or without brain metastases at baseline.

Major finding: In patients with and without baseline brain metastasis, lorlatinib vs. crizotinib improved the 12-month PFS (78% vs. 22% and 78% vs. 45%, respectively) and 12-month cumulative incidence of CNS progression (7% vs. 72% and 1% vs. 18%, respectively).

Study details: The data come from a post hoc analysis of the CROWN trial including patients with ALK+ NSCLC and with (n = 78) or without (n = 218) brain metastasis at baseline.

Disclosures: The CROWN trial was funded by Pfizer. Many authors reported ties with multiple pharmaceutical companies, including Pfizer.

Source: Solomon BJ et al. Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non–small-cell lung cancer from the phase III CROWN study. J Clin Oncol. 2022 (May 23). Doi:  10.1200/JCO.21.02278

Key clinical point: Aumolertinib vs. gefitinib as the first-line therapy significantly improves progression-free survival (PFS) in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutation (i.e., exon 19 deletion or L858R mutation).

Major finding: The aumolertinib vs. gefitinib group had a significantly longer median PFS (19.3 vs. 9.9 months; hazard ratio [HR] 0.46; P < .0001). The PFS advantage of aumolertinib over gefitinib was substantial in the subgroup of patients with central nervous system metastases (15.3 vs. 8.2 months; HR 0.38; P < .0001).

Study details: This randomized, double-blind, multicenter, phase 3 AENEAS trial included 429 patients with EGFR-mutated NSCLC who were randomly assigned (1:1) to receive either the first-line aumolertinib or gefitinib once daily orally.

Disclosures: The study was funded by Hansoh Pharmaceutical Group Co, Ltd. Many authors reported ties with one or more pharmaceutical companies, including Hansoh Pharma.

Source: Lu S et al. AENEAS: A randomized phase III trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastatic non–small-cell lung cancer with EGFR exon 19 deletion or L858R mutations. J Clin Oncol. 2022 (May 17). Doi: 10.1200/JCO.21.02641

Key clinical point: Aumolertinib vs. gefitinib as the first-line therapy significantly improves progression-free survival (PFS) in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutation (i.e., exon 19 deletion or L858R mutation).

Major finding: The aumolertinib vs. gefitinib group had a significantly longer median PFS (19.3 vs. 9.9 months; hazard ratio [HR] 0.46; P < .0001). The PFS advantage of aumolertinib over gefitinib was substantial in the subgroup of patients with central nervous system metastases (15.3 vs. 8.2 months; HR 0.38; P < .0001).

Study details: This randomized, double-blind, multicenter, phase 3 AENEAS trial included 429 patients with EGFR-mutated NSCLC who were randomly assigned (1:1) to receive either the first-line aumolertinib or gefitinib once daily orally.

Disclosures: The study was funded by Hansoh Pharmaceutical Group Co, Ltd. Many authors reported ties with one or more pharmaceutical companies, including Hansoh Pharma.

Source: Lu S et al. AENEAS: A randomized phase III trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastatic non–small-cell lung cancer with EGFR exon 19 deletion or L858R mutations. J Clin Oncol. 2022 (May 17). Doi: 10.1200/JCO.21.02641

Key clinical point: Aumolertinib vs. gefitinib as the first-line therapy significantly improves progression-free survival (PFS) in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutation (i.e., exon 19 deletion or L858R mutation).

Major finding: The aumolertinib vs. gefitinib group had a significantly longer median PFS (19.3 vs. 9.9 months; hazard ratio [HR] 0.46; P < .0001). The PFS advantage of aumolertinib over gefitinib was substantial in the subgroup of patients with central nervous system metastases (15.3 vs. 8.2 months; HR 0.38; P < .0001).

Study details: This randomized, double-blind, multicenter, phase 3 AENEAS trial included 429 patients with EGFR-mutated NSCLC who were randomly assigned (1:1) to receive either the first-line aumolertinib or gefitinib once daily orally.

Disclosures: The study was funded by Hansoh Pharmaceutical Group Co, Ltd. Many authors reported ties with one or more pharmaceutical companies, including Hansoh Pharma.

Source: Lu S et al. AENEAS: A randomized phase III trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastatic non–small-cell lung cancer with EGFR exon 19 deletion or L858R mutations. J Clin Oncol. 2022 (May 17). Doi: 10.1200/JCO.21.02641

Key clinical point: First-line tiragolumab plus atezolizumab vs. placebo plus atezolizumab is associated with a better objective response rate (ORR) and progression-free survival (PFS) in patients with programmed cell death-ligand 1 (PD-L1)-positive, recurrent, or metastatic nonsmall cell lung cancer (NSCLC).

Major finding: The tiragolumab vs. placebo group demonstrated a superior ORR (31.3% vs. 16.2%; P = .031) and median PFS (5.4 vs. 3.6 months; stratified hazard ratio 0.57; P = .015). The rates of serious treatment-related adverse events in the tiragolumab and placebo groups were 21% and 18%, respectively.

Study details: This phase 2 randomized, double-blind, placebo-controlled CITYSCAPE trial included chemotherapy-naive patients with PD-L1-positive recurrent or metastatic NSCLC (with no EGFR or ALK alterations) who were randomly assigned to receive either tiragolumab plus atezolizumab (n = 67) or placebo plus atezolizumab (n = 68) once every 3 weeks.

Disclosures: The study was funded by F Hoffmann-La Roche and Genentech. M Cobo, N Secen, and X Yang declared no competing interests. The other authors reported ties with one or more pharmaceutical companies, including employment or stock options in the funding companies.

Source: Cho BC et al. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): Primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol. 2022;23(6):781-792 (May 13). Doi: 10.1016/S1470-2045(22)00226-1

Key clinical point: First-line tiragolumab plus atezolizumab vs. placebo plus atezolizumab is associated with a better objective response rate (ORR) and progression-free survival (PFS) in patients with programmed cell death-ligand 1 (PD-L1)-positive, recurrent, or metastatic nonsmall cell lung cancer (NSCLC).

Major finding: The tiragolumab vs. placebo group demonstrated a superior ORR (31.3% vs. 16.2%; P = .031) and median PFS (5.4 vs. 3.6 months; stratified hazard ratio 0.57; P = .015). The rates of serious treatment-related adverse events in the tiragolumab and placebo groups were 21% and 18%, respectively.

Study details: This phase 2 randomized, double-blind, placebo-controlled CITYSCAPE trial included chemotherapy-naive patients with PD-L1-positive recurrent or metastatic NSCLC (with no EGFR or ALK alterations) who were randomly assigned to receive either tiragolumab plus atezolizumab (n = 67) or placebo plus atezolizumab (n = 68) once every 3 weeks.

Disclosures: The study was funded by F Hoffmann-La Roche and Genentech. M Cobo, N Secen, and X Yang declared no competing interests. The other authors reported ties with one or more pharmaceutical companies, including employment or stock options in the funding companies.

Source: Cho BC et al. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): Primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol. 2022;23(6):781-792 (May 13). Doi: 10.1016/S1470-2045(22)00226-1

Key clinical point: First-line tiragolumab plus atezolizumab vs. placebo plus atezolizumab is associated with a better objective response rate (ORR) and progression-free survival (PFS) in patients with programmed cell death-ligand 1 (PD-L1)-positive, recurrent, or metastatic nonsmall cell lung cancer (NSCLC).

Major finding: The tiragolumab vs. placebo group demonstrated a superior ORR (31.3% vs. 16.2%; P = .031) and median PFS (5.4 vs. 3.6 months; stratified hazard ratio 0.57; P = .015). The rates of serious treatment-related adverse events in the tiragolumab and placebo groups were 21% and 18%, respectively.

Study details: This phase 2 randomized, double-blind, placebo-controlled CITYSCAPE trial included chemotherapy-naive patients with PD-L1-positive recurrent or metastatic NSCLC (with no EGFR or ALK alterations) who were randomly assigned to receive either tiragolumab plus atezolizumab (n = 67) or placebo plus atezolizumab (n = 68) once every 3 weeks.

Disclosures: The study was funded by F Hoffmann-La Roche and Genentech. M Cobo, N Secen, and X Yang declared no competing interests. The other authors reported ties with one or more pharmaceutical companies, including employment or stock options in the funding companies.

Source: Cho BC et al. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): Primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol. 2022;23(6):781-792 (May 13). Doi: 10.1016/S1470-2045(22)00226-1

Key clinical point: Patients with squamous cell lung carcinoma (SqCLC) and moderate-to-severe diabetes may have a higher risk for all-cause mortality than those with SqCLC and mild diabetes.

Major finding: Patients with SqCLC and moderate to severe diabetes had a 17% higher risk for all-cause death than those with SqCLC and mild diabetes (adjusted hazard ratio 1.17; P = .0005).

Study details: The data come from a retrospective cohort study including patients with both SqCLC and diabetes (n = 5742) from the Taiwan Cancer Registry database.

Disclosures: The study was funded by grants from Lo-Hsu Medical Foundation, LotungPoh-Ai Hospital, and Fu Jen Catholic University. The authors declared no conflicts of interest.

Source: Su C-H et al. Association of diabetes severity and mortality with lung squamous cell carcinoma. Cancers (Basel). 2022;14(10):2553 (May 22). Doi: 10.3390/cancers14102553

Key clinical point: Patients with squamous cell lung carcinoma (SqCLC) and moderate-to-severe diabetes may have a higher risk for all-cause mortality than those with SqCLC and mild diabetes.

Major finding: Patients with SqCLC and moderate to severe diabetes had a 17% higher risk for all-cause death than those with SqCLC and mild diabetes (adjusted hazard ratio 1.17; P = .0005).

Study details: The data come from a retrospective cohort study including patients with both SqCLC and diabetes (n = 5742) from the Taiwan Cancer Registry database.

Disclosures: The study was funded by grants from Lo-Hsu Medical Foundation, LotungPoh-Ai Hospital, and Fu Jen Catholic University. The authors declared no conflicts of interest.

Source: Su C-H et al. Association of diabetes severity and mortality with lung squamous cell carcinoma. Cancers (Basel). 2022;14(10):2553 (May 22). Doi: 10.3390/cancers14102553

Key clinical point: Patients with squamous cell lung carcinoma (SqCLC) and moderate-to-severe diabetes may have a higher risk for all-cause mortality than those with SqCLC and mild diabetes.

Major finding: Patients with SqCLC and moderate to severe diabetes had a 17% higher risk for all-cause death than those with SqCLC and mild diabetes (adjusted hazard ratio 1.17; P = .0005).

Study details: The data come from a retrospective cohort study including patients with both SqCLC and diabetes (n = 5742) from the Taiwan Cancer Registry database.

Disclosures: The study was funded by grants from Lo-Hsu Medical Foundation, LotungPoh-Ai Hospital, and Fu Jen Catholic University. The authors declared no conflicts of interest.

Source: Su C-H et al. Association of diabetes severity and mortality with lung squamous cell carcinoma. Cancers (Basel). 2022;14(10):2553 (May 22). Doi: 10.3390/cancers14102553

The combination of neoadjuvant chemotherapy with immunotherapy led to significant improvements in survival for patients with resectable stage IIIA-B non–small cell lung cancer (NSCLC), according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.

“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.

The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.

In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m² and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.

At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).

The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.

The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.

This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).

The combination of neoadjuvant chemotherapy with immunotherapy led to significant improvements in survival for patients with resectable stage IIIA-B non–small cell lung cancer (NSCLC), according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.

“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.

The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.

In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m² and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.

At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).

The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.

The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.

This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).

The combination of neoadjuvant chemotherapy with immunotherapy led to significant improvements in survival for patients with resectable stage IIIA-B non–small cell lung cancer (NSCLC), according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.

“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.

The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.

In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m² and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.

At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).

The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.

The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.

This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).

Adagrasib, an investigational drug that acts as a KRASG12C inhibitor, has shown durable clinical benefit in patients with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.

“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.

“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.

New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.

Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.

If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.  

Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
 

Published clinical data

The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.

It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.

Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.

On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.

Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.

Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.

“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.

Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
 

CNS metastases

At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.

As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.

The study was funded by Mirati Therapeutics.

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

Adagrasib, an investigational drug that acts as a KRASG12C inhibitor, has shown durable clinical benefit in patients with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.

“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.

“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.

New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.

Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.

If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.  

Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
 

Published clinical data

The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.

It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.

Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.

On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.

Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.

Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.

“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.

Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
 

CNS metastases

At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.

As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.

The study was funded by Mirati Therapeutics.

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

Adagrasib, an investigational drug that acts as a KRASG12C inhibitor, has shown durable clinical benefit in patients with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.

“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.

“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.

New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.

Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.

If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.  

Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
 

Published clinical data

The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.

It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.

Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.

On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.

Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.

Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.

“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.

Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
 

CNS metastases

At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.

As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.

The study was funded by Mirati Therapeutics.

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

Among patients with resectable non–small cell lung cancer (NSCLC), neoadjuvant nivolumab combined with chemotherapy led to significantly longer event-free survival and more frequent pathological complete response in patients than chemotherapy alone.

“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.

Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.

About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.

In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
 

Results from CheckMate 816

CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.

Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.

After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).

A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).

Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.

The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.

There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.

The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.

Among patients with resectable non–small cell lung cancer (NSCLC), neoadjuvant nivolumab combined with chemotherapy led to significantly longer event-free survival and more frequent pathological complete response in patients than chemotherapy alone.

“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.

Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.

About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.

In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
 

Results from CheckMate 816

CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.

Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.

After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).

A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).

Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.

The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.

There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.

The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.

Among patients with resectable non–small cell lung cancer (NSCLC), neoadjuvant nivolumab combined with chemotherapy led to significantly longer event-free survival and more frequent pathological complete response in patients than chemotherapy alone.

“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.

Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.

About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.

In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
 

Results from CheckMate 816

CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.

Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.

After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).

A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).

Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.

The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.

There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.

The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.