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Article: 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

TitleUpdated 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
Authors
Issue Date2019
Citation
Journal of Clinical Oncology, 2019, v. 37, n. 7, p. 537-546 How to Cite?
AbstractPURPOSE 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. 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. 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). 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.
Persistent Identifierhttp://hdl.handle.net/10722/326485
ISSN
2023 Impact Factor: 42.1
2023 SCImago Journal Rankings: 10.639
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorReck, Martin-
dc.contributor.authorRodríguez-Abreu, Delvys-
dc.contributor.authorRobinson, Andrew G.-
dc.contributor.authorHui, Rina-
dc.contributor.authorCsoszi, Tibor-
dc.contributor.authorFülöp, Andrea-
dc.contributor.authorGottfried, Maya-
dc.contributor.authorPeled, Nir-
dc.contributor.authorTafreshi, Ali-
dc.contributor.authorCuffe, Sinead-
dc.contributor.authorO’Brien, Mary-
dc.contributor.authorRao, Suman-
dc.contributor.authorHotta, Katsuyuki-
dc.contributor.authorVandormael, Kristel-
dc.contributor.authorRiccio, Antonio-
dc.contributor.authorYang, Jing-
dc.contributor.authorCatherine Pietanza, M.-
dc.contributor.authorBrahmer, Julie R.-
dc.date.accessioned2023-03-10T02:19:37Z-
dc.date.available2023-03-10T02:19:37Z-
dc.date.issued2019-
dc.identifier.citationJournal of Clinical Oncology, 2019, v. 37, n. 7, p. 537-546-
dc.identifier.issn0732-183X-
dc.identifier.urihttp://hdl.handle.net/10722/326485-
dc.description.abstractPURPOSE 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. 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. 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). 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.-
dc.languageeng-
dc.relation.ispartofJournal of Clinical Oncology-
dc.titleUpdated 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-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1200/JCO.18.00149-
dc.identifier.pmid30620668-
dc.identifier.scopuseid_2-s2.0-85064128148-
dc.identifier.volume37-
dc.identifier.issue7-
dc.identifier.spage537-
dc.identifier.epage546-
dc.identifier.eissn1527-7755-
dc.identifier.isiWOS:000460356200002-

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