Pembrolizumab plus Chemotherapy for Squamous Non–Small‐Cell Lung Cancer

By L. Paz-Ares, A. Luft, D. Vicente, A. Tafreshi, M. Gümüş, J. Mazières, B. Hermes, F. Senler, T. Csőszi, A. Fülöp and 12 more. New England Journal of Medicine, 2018

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Background Standard first‐line therapy for metastatic, squamous non–small‐cell lung cancer (NSCLC) is platinum‐based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD‐L1] expression on ≥50% of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC. Methods In this double‐blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin‐bound [nab]–paclitaxel for the first 4 cycles. Primary end points were overall survival and progression‐free survival. Results After a median follow‐up of 7.8 months, the median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab‐combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo‐combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD‐L1 expression. The median progression‐free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab‐combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo‐combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8% of the patients in the pembrolizumab‐combination group and in 68.2% of the patients in the placebo‐combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab‐combination group than in the placebo‐combination group (13.3% vs. 6.4%). Conclusions In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab‐paclitaxel resulted in significantly longer overall survival and progression‐free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE‐407 ClinicalTrials.gov number, NCT02775435.)

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/1b7635b52c881cbeb9c5a11108820bfcab193329

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Citations in the corpus

• Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2018, background): “KEYNOTE-407 is a randomised, placebo-controlled study of patients with metastatic squamous NSCLC [99].”
• Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022, background): “Later, in two phase 3 clinical studies (KEYNOTE-189 and KEYNOTE-407), pembrolizumab combined with standard chemotherapy led to a better overall survival (OS) and PFS in NSCLC patients, relative to chemotherapy monotherapy [53, 54].”
• Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence (2020, background): “On 30 October 2018, the FDA expanded approval of pembrolizumab as a first-line therapy to metastatic squamous NSCLC in combination with carboplatin with paclitaxel/nab-paclitaxel irrespective of PD-L1 status based on the improved ORR, PFS and OS in a patient with pembrolizumab than without from Keyn”
• 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, methodology): “gov identifier: NCT02775435) study.(19) Together with our current analyses, these data show that for all patients with advanced NSCLC without EGFR/ ALK alterations, a first-line treatment regimen containing pembrolizumab (either as monotherapy or in combination with platinum chemotherapy) is availab”
• Evaluating eligibility criteria of oncology trials using real-world data and AI (2021, background): “Relaxing restrictive eligibility criteria has the important benefit of making clinical trials more inclusive for diverse populations (Supplementary Tables 6–8).”