[HTML][HTML] Pembrolizumab plus chemotherapy for squamous non–small-cell lung cancer
L Paz-Ares, A Luft, D Vicente, A Tafreshi… - … England Journal of …, 2018 - Mass Medical Soc
New England Journal of Medicine, 2018•Mass Medical Soc
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 …
(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 …
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.)
The New England Journal Of Medicine