KEYNOTE-407: First-Line Pembrolizumab Plus Chemotherapy in Metastatic Squamous NSCLC
As reported at the recent International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer and in The New England Journal of Medicine by Paz-Ares et al, the phase III KEYNOTE-407 trial has shown that the addition of pembrolizumab to platinum-based chemotherapy significantly improved overall and progression-free survival in patients with previously untreated metastatic squamous non–small cell lung cancer (NSCLC).
In the double-blind trial, 559 patients from 125 sites in 17 countries were randomized between August 2016 and December 2017 to receive pembrolizumab at 200 mg (n = 278) or placebo (n = 281) on day 1 of 3-week cycles for up to 35 cycles, plus carboplatin (AUC = 6 on day 1) and either paclitaxel (200 mg/m2 on day 1) or nab-paclitaxel (Abraxane; 100 mg/m2 on days 1, 8, and 15) for the first 4 cycles. Randomization was stratified according to programmed cell death ligand 1 (PD-L1) tumor proportion score (≥ 1% [63% of patients] vs < 1%), taxane used (paclitaxel in 60% of patients), and geographic regions of East Asia (19% of patients) vs the rest of the world.
The primary endpoints were overall survival and progression-free survival on independent central review.
Survival and Adverse Events
Median follow-up was 7.8 months. Median overall survival was 15.9 months (95% confidence interval [CI] = 13.2 months to not reached) in the pembrolizumab group vs 11.3 months (95% CI = 9.5–14.8 months) in the placebo group (hazard ratio [HR] = 0.64, P < .001). The overall survival benefit was consistent across levels of PD-L1 expression, with hazard ratios of 0.61 (95% CI = 0.38–0.98) among patients with expression < 1% and 0.65 (95% CI = 0.45–0.92) among those with expression ≥ 1%. Hazard ratios were 0.44 (95% CI = 0.22–0.89) among patients from East Asia and 0.69 (95% CI = 0.51–0.93) among those from the rest of the world; and 0.67 (95% CI = 0.48–0.93) among patients receiving paclitaxel and 0.59 (95% CI = 0.36–0.98) among those receiving nab-paclitaxel. Median progression-free survival was 6.4 months vs 4.8 months (HR = 0.56, P < .001), with the benefit of pembrolizumab observed across subgroups.
Adverse events of grade ≥ 3 occurred in 69.8% of the pembrolizumab group and in 68.2% of the placebo group. Adverse events of any grade led to discontinuation of any study treatment in 23.4% vs 11.8% and to discontinuation of pembrolizumab vs placebo in 17.3% vs 7.9%. Adverse events led to death in 8.3% vs 6.4% of patients, with death considered to be potentially related to treatment in 3.6% vs 2.1%. Potential immune-related adverse events occurred in 28.8% (10.8% grade ≥ 3) vs 8.6% (3.2% grade ≥ 3).
The investigators concluded, “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.”
The study was funded by Merck Sharp & Dohme.
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