Pembrolizumab Plus Chemotherapy Approved to Treat Metastatic Squamous NSCLC

Earlier this week, the FDA approved pembrolizumab (Keytruda) in combination with carboplatin and either paclitaxel or nab-paclitaxel for the first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC).

The approval was based on findings from the KEYNOTE-407 trial, a randomized, double-blind, multicenter, placebo-controlled study which investigated the efficacy of the combination treatment in patients with metastatic squamous NSCLC regardless of tumor PD-L1 expression. Patients were randomized to receive pembrolizumab 200mg and carboplatin every 3 weeks for 4 cycles, plus paclitaxel every 3 weeks for 4 cycles or nab-paclitaxel on days 1, 8, and 15 of every 3-week cycle for 4 cycles.

The trial found that pembrolizumab in combination with chemotherapy significantly improved overall survival and reduced the risk of death by 36% compared with chemotherapy alone (HR=0.64 [95% CI, 0.49, 0.85]; P = 0.0017).

“Today’s approval expands our current lung cancer indications to include combination treatment in patients with squamous cell carcinoma, a type of lung cancer that is particularly difficult to treat,” said Roger M. Perlmutter, MD, president of Merck Research Laboratories.

The safety of the combination treatment was investigated in 101 patients at the first interim analysis of the trial. The most frequent (≥2%)serious adverse reactions were febrile neutropenia (6%), pneumonia (6%), and urinary tract infection (3%).

“With this important approval, more patients will have the opportunity to benefit from immunotherapy,” said Balazs Halmos, MD, director of the multidisciplinary thoracic oncology program at the Montefiore Einstein Center for Cancer Care.

This approval is the first time an anti-PD-1 treatment regimen was approved as a first-line treatment of squamous NSCLC regardless of tumor PD-L1 expression. Due to this newly approved treatment option, all appropriate patients with metastatic squamous NSCLC as well as appropriate patients with metastatic nonsquamous NSCLC and no EGFR or ALK genomic tumor mutations are now eligible for the pembrolizumab combination treatment as their first-line treatment option.