Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer

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http://hdl.handle.net/10138/298862

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KEYNOTE-189 Investigators , Gandhi , L & Myllärniemi , M 2018 , ' Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer ' , New England Journal of Medicine , vol. 378 , no. 22 , pp. 2078-2092 . https://doi.org/10.1056/NEJMoa1801005

Title: Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer
Author: KEYNOTE-189 Investigators; Gandhi, L.; Myllärniemi, Marjukka
Contributor: University of Helsinki, Department of Medicine
Date: 2018-05-31
Language: eng
Number of pages: 15
Belongs to series: New England Journal of Medicine
ISSN: 0028-4793
URI: http://hdl.handle.net/10138/298862
Abstract: BACKGROUND First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial. METHODS In this double-blind, phase 3 trial, we randomly assigned (in a 2: 1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression. The primary end points were overall survival and progression-free survival, as assessed by blinded, independent central radiologic review. RESULTS After a median follow-up of 10.5 months, the estimated rate of overall survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in the pembrolizumab-combination group versus 49.4% (95% CI, 42.1 to 56.2) in the placebocombination group (hazard ratio for death, 0.49; 95% CI, 0.38 to 0.64; P<0.001). Improvement in overall survival was seen across all PD-L1 categories that were evaluated. Median progression-free survival was 8.8 months (95% CI, 7.6 to 9.2) in the pembrolizumab-combination group and 4.9 months (95% CI, 4.7 to 5.5) in the placebo-combination group (hazard ratio for disease progression or death, 0.52; 95% CI, 0.43 to 0.64; P<0.001). Adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group. CONCLUSIONS In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.
Subject: RANDOMIZED CONTROLLED-TRIAL
PEMETREXED PLUS
OPEN-LABEL
INDUCTION TREATMENT
PHASE-III
DOCETAXEL
CISPLATIN
NIVOLUMAB
1ST-LINE
THERAPY
3122 Cancers
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