Pembrolizumab (Keytruda®, Merck) in combination with chemotherapy was associated with longer overall survival (OS) and progression-free survival (PFS) when compared to placebo plus chemotherapy in patients with untreated metastatic squamous cell non-small cell lung cancer (NSCLC).

“Standard first-line therapy for metastatic, squamous NSCLC is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50% of tumour cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC.”

The Phase III, multi-centre, double-blind controlled KEYNOTE-407 (NCT02775435) study randomised 559 treatment-naïve, untreated metastatic, squamous NSCLC patients in a 1:1 fashion to either receive four cycles of pembrolizumab plus chemotherapy with carboplatin and paclitaxel or nab-paclitaxel followed by maintenance pembrolizumab vs four cycles of placebo plus chemotherapy followed by maintenance placebo. The primary efficacy endpoints were OS and PFS.

At a median follow-up of 7.8 months, the median OS in the pembrolizumab plus chemotherapy arm was 15.9 months (95% CI, 13.2-not reached) vs 11.3 months (95% CI, 9.5-14.8) in the placebo plus chemotherapy arm (HR=0.64; 95% CI, 0.49-0.85; p<0.001), an OS benefit that was consistent regardless of the PD-L1 level expression. The median PFS measured 6.4 months (95% CI, 6.2-8.3) vs 4.8 months (95% CI, 4.3 to 5.7) for the pembrolizumab plus chemotherapy vs placebo plus chemotherapy groups, respectively (HR=0.56; 95% CI, 0.45-0.70; p<0.001).

Grade ≥3 adverse events (AEs) occurred in 69.8% and 68.2% of patients in the pembrolizumab plus chemotherapy-group vs the placebo plus chemotherapy-group, respectively. Treatment discontinuation for AEs occurred in 13.3% and 6.4% of patients, respectively.

Reference

Paz-Ares L, et al. N Engl J Med. 2018; doi: 10.1056/NEJMoa1810865.