KEYNOTE-407: First-Line Pembrolizumab Plus Chemotherapy in Metastatic Squamous NSCLC


Key Points

  • The addition of pembrolizumab to platinum-based chemotherapy significantly improved overall survival and progression-free survival.
  • Benefits appeared to be consistent across levels of PD-L1 expression.

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.