Keytruda plus Alimta Combination Approved for First-Line Therapy of Metastatic NSCLC

April 2019, Vol 10, No 2 - FDA Approvals, News & Updates


On January 31, 2019, the FDA approved the combination of pemetrexed (Alimta; Eli Lilly) plus pembrolizumab (Keytruda; Merck) and platinum-based chemotherapy for first-line treatment of patients with metastatic nonsquamous non–small-cell lung cancer (NSCLC) and no EGFR or ALK mutations. This regimen was initially granted accelerated approval in June 2018 for this indication based on tumor response rates and progression-free survival (PFS) data from a phase 2 clinical trial. Continued approval was dependent on verification of data from a phase 3 clinical trial.

This full approval was based on the phase 3, randomized, double-blind, KEYNOTE-189 study of 616 patients with metastatic nonsquamous NSCLC, regardless of PD-1 expression, and no EGFR or ALK mutations. Patients were randomized to pemetrexed plus pembrolizumab and platinum-based chemotherapy or pemetrexed plus placebo and platinum-based chemotherapy.

The median PFS in the pemetrexed plus pembrolizumab and carboplatin arm was 8.8 months versus 4.9 months in the placebo group (P <.0001). The median overall survival in the pemetrexed plus pembrolizumab plus platinum chemotherapy arm had not yet been reached versus 11.3 months in the placebo arm (P <.0001).

The most common (≥20%) adverse events with pemetrexed plus pembro­lizumab and platinum chemotherapy were nausea, fatigue, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia.