Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non–small cell lung cancer without tumor PD‐L1 expression: A pooled analysis of 3 randomized controlled trials

Background Pembrolizumab plus platinum‐based chemotherapy has demonstrated improved clinical outcomes over chemotherapy alone in patients with previously untreated advanced/metastatic non–small cell lung cancer (NSCLC), regardless of tumor programmed death ligand 1 (PD‐L1) expression. This study pooled data from 3 randomized controlled trials to evaluate outcomes with pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced/metastatic NSCLC negative for PD‐L1 (ie, a tumor proportion score < 1%). Methods Individual patient data were pooled from KEYNOTE‐021 cohort G (nonsquamous; NCT02039674), KEYNOTE‐189 (nonsquamous; NCT02578680 and NCT03950674), and KEYNOTE‐407 (squamous; NCT02775435). Treatment comprised pembrolizumab plus chemotherapy (pemetrexed and platinum for nonsquamous histology and carboplatin and paclitaxel/nab‐paclitaxel for squamous histology) or chemotherapy alone. Responses were assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 by blinded, independent, central review. No α was assigned to this descriptive, exploratory analysis. Results Four hundred forty‐four of the 1328 patients (33.4%) who were enrolled across the 3 trials had PD‐L1‒negative tumors (256 on pembrolizumab plus chemotherapy [nonsquamous, n = 155; squamous, n = 94; other, n = 7] and 188 on chemotherapy alone [nonsquamous, n = 83; squamous, n = 99; other, n = 6]). The median time from randomization to the data cutoff was 28.0 months (range, 14.7‐55.4 months). Pembrolizumab plus chemotherapy improved overall survival (OS; hazard ratio [HR], 0.63; 95% CI, 0.50‐0.79) and progression‐free survival (HR, 0.68; 95% CI, 0.56‐0.83) over chemotherapy. Sixteen patients in the pembrolizumab plus chemotherapy arm completed 2 years of treatment; the objective response rate was 87.5% (95% CI, 61.7%‐98.4%), and the 3‐year OS rate was 100%. Adverse events (AEs) were experienced by 99.2% of the patients who received pembrolizumab plus chemotherapy and by 98.9% of the patients who received chemotherapy alone, with grade 3 or higher AEs occurring in 71.4% and 72.0%, respectively; immune‐mediated AEs and infusion reactions were experienced by 29.0% and 12.4%, respectively. Conclusions Pembrolizumab plus chemotherapy demonstrated response and survival improvements with manageable safety in comparison with chemotherapy alone in PD‐L1‒negative advanced/metastatic NSCLC, and it is a standard‐of‐care first‐line therapy for patients with advanced NS