Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater.
Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater.
- 2019
Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008
CONCLUSION: With prolonged follow-up, first-line pembrolizumab monotherapy continues to demonstrate an OS benefit over chemotherapy in patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations, despite crossover from the control arm to pembrolizumab as subsequent therapy. PATIENTS AND METHODS: Patients were randomly assigned to pembrolizumab 200 mg every 3 weeks (for up to 2 years) or investigator's choice of platinum-based chemotherapy (four to six cycles). Patients assigned to chemotherapy could cross over to pembrolizumab upon meeting eligibility criteria. The primary end point was progression-free survival; OS was an important key secondary end point. Crossover adjustment analysis was done using the following three methods: simplified two-stage method, rank-preserving structural failure time, and inverse probability of censoring weighting. PURPOSE: In the randomized, open-label, phase III KEYNOTE- 024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non- small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab. RESULTS: Three hundred five patients were randomly assigned (pembrolizumab, n = 154; chemotherapy, n = 151). At data cutoff (July 10, 2017; median follow-up, 25.2 months), 73 patients in the pembrolizumab arm and 96 in the chemotherapy arm had died. Median OS was 30.0 months (95% CI, 18.3 months to not reached) with pembrolizumab and 14.2 months (95% CI, 9.8 to 19.0 months) with chemotherapy (hazard ratio, 0.63; 95% CI, 0.47 to 0.86). Eighty-two patients assigned to chemotherapy crossed over on study to receive pembrolizumab. When adjusted for crossover using the two-stage method, the hazard ratio for OS for pembrolizumab versus chemotherapy was 0.49 (95% CI, 0.34 to 0.69); results using rank-preserving structural failure time and inverse probability of censoring weighting were similar. Treatment-related grade 3 to 5 adverse events were less frequent with pembrolizumab compared with chemotherapy (31.2% v 53.3%, respectively).
English
0732-183X
10.1200/JCO.18.00149 [doi]
*Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
*Antineoplastic Agents, Immunological/ad [Administration & Dosage]
*Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
*B7-H1 Antigen/ai [Antagonists & Inhibitors]
*Carboplatin/ad [Administration & Dosage]
*Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
*Cisplatin/ad [Administration & Dosage]
*Lung Neoplasms/dt [Drug Therapy]
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
Antineoplastic Agents, Immunological/ae [Adverse Effects]
Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
B7-H1 Antigen/im [Immunology]
Carboplatin/ae [Adverse Effects]
Carcinoma, Non-Small-Cell Lung/im [Immunology]
Carcinoma, Non-Small-Cell Lung/mo [Mortality]
Carcinoma, Non-Small-Cell Lung/pa [Pathology]
Cisplatin/ae [Adverse Effects]
Cross-Over Studies
Disease Progression
Female
Humans
Lung Neoplasms/im [Immunology]
Lung Neoplasms/mo [Mortality]
Lung Neoplasms/pa [Pathology]
Male
Middle Aged
Neoplasm Staging
Progression-Free Survival
Time Factors
Medstar Franklin Square Medical Center
Journal Article
Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008
CONCLUSION: With prolonged follow-up, first-line pembrolizumab monotherapy continues to demonstrate an OS benefit over chemotherapy in patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations, despite crossover from the control arm to pembrolizumab as subsequent therapy. PATIENTS AND METHODS: Patients were randomly assigned to pembrolizumab 200 mg every 3 weeks (for up to 2 years) or investigator's choice of platinum-based chemotherapy (four to six cycles). Patients assigned to chemotherapy could cross over to pembrolizumab upon meeting eligibility criteria. The primary end point was progression-free survival; OS was an important key secondary end point. Crossover adjustment analysis was done using the following three methods: simplified two-stage method, rank-preserving structural failure time, and inverse probability of censoring weighting. PURPOSE: In the randomized, open-label, phase III KEYNOTE- 024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non- small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab. RESULTS: Three hundred five patients were randomly assigned (pembrolizumab, n = 154; chemotherapy, n = 151). At data cutoff (July 10, 2017; median follow-up, 25.2 months), 73 patients in the pembrolizumab arm and 96 in the chemotherapy arm had died. Median OS was 30.0 months (95% CI, 18.3 months to not reached) with pembrolizumab and 14.2 months (95% CI, 9.8 to 19.0 months) with chemotherapy (hazard ratio, 0.63; 95% CI, 0.47 to 0.86). Eighty-two patients assigned to chemotherapy crossed over on study to receive pembrolizumab. When adjusted for crossover using the two-stage method, the hazard ratio for OS for pembrolizumab versus chemotherapy was 0.49 (95% CI, 0.34 to 0.69); results using rank-preserving structural failure time and inverse probability of censoring weighting were similar. Treatment-related grade 3 to 5 adverse events were less frequent with pembrolizumab compared with chemotherapy (31.2% v 53.3%, respectively).
English
0732-183X
10.1200/JCO.18.00149 [doi]
*Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
*Antineoplastic Agents, Immunological/ad [Administration & Dosage]
*Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
*B7-H1 Antigen/ai [Antagonists & Inhibitors]
*Carboplatin/ad [Administration & Dosage]
*Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
*Cisplatin/ad [Administration & Dosage]
*Lung Neoplasms/dt [Drug Therapy]
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
Antineoplastic Agents, Immunological/ae [Adverse Effects]
Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
B7-H1 Antigen/im [Immunology]
Carboplatin/ae [Adverse Effects]
Carcinoma, Non-Small-Cell Lung/im [Immunology]
Carcinoma, Non-Small-Cell Lung/mo [Mortality]
Carcinoma, Non-Small-Cell Lung/pa [Pathology]
Cisplatin/ae [Adverse Effects]
Cross-Over Studies
Disease Progression
Female
Humans
Lung Neoplasms/im [Immunology]
Lung Neoplasms/mo [Mortality]
Lung Neoplasms/pa [Pathology]
Male
Middle Aged
Neoplasm Staging
Progression-Free Survival
Time Factors
Medstar Franklin Square Medical Center
Journal Article