FDA Approves Alimta plus Keytruda as First-Line Treatment for Metastatic NSCLC
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) with no EGFR or ALK mutations. The regimen was initially granted accelerated approval by the FDA 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 upon verification and description of clinical benefit, which has now been demonstrated in a phase 3 trial.
This full approval was based on the phase 3, randomized, double-blind, KEYNOTE-189 clinical trial of 616 patients with metastatic nonsquamous NSCLC, regardless of PD-1 expression, and with no EGFR or ALK mutations. Patients enrolled in this trial were randomized in a 2:1 ratio to pemetrexed plus pembrolizumab and platinum-based chemotherapy or pemetrexed plus placebo and platinum-based chemotherapy.
Results showed that patients in the experimental group had significantly longer overall survival (OS) and PFS than those in the control group. The median PFS in the pemetrexed plus pembrolizumab and carboplatin group was 8.8 months versus 4.9 months in the placebo group (P <.0001). Median OS in the pemetrexed plus pembrolizumab plus platinum chemotherapy group had not yet been reached versus 11.3 months in the placebo group (P <.0001).
The most common (≥20%) adverse events reported with pemetrexed in combination with pembrolizumab and platinum-based chemotherapy were nausea, fatigue, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia.