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.

MedStar author(s):
Citation: Journal of Clinical Oncology. 37(7):537-546, 2019 03 01.PMID: 30620668Institution: Medstar Franklin Square Medical CenterForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *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 FactorsYear: 2019Local holdings: Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008ISSN:
  • 0732-183X
Name of journal: Journal of clinical oncology : official journal of the American Society of Clinical OncologyAbstract: 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).All authors: Brahmer JR, Csoszi T, Cuffe S, Fulop A, Gottfried M, Hotta K, Hui R, O'Brien M, Peled N, Pietanza MC, Rao S, Reck M, Riccio A, Robinson AG, Rodriguez-Abreu D, Tafreshi A, Vandormael K, Yang JOriginally published: Journal of Clinical Oncology. :JCO1800149, 2019 Jan 08Fiscal year: FY2019Digital Object Identifier: Date added to catalog: 2019-01-18
Holdings
Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 30620668 Available 30620668

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).

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