FDA Expands Pemetrexed Indication With Pembrolizumab and Chemotherapy in First-Line Treatment of NSCLC
Posted: Thursday, January 31, 2019
Today, the U.S. Food and Drug Administration (FDA) granted approval of a new indication for pemetrexed (Alimta) for injection in combination with pembrolizumab (Keytruda) and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations. This indication was approved based on data from the phase III KEYNOTE-189 trial (ClinicalTrials.gov identifier NCT02578680), which enrolled patients regardless of PD-L1 expression and had dual primary endpoints of overall and progression-free survival.
KEYNOTE-189 was a randomized, double-blind, placebo-controlled, phase III study that evaluated pemetrexed in combination with pembrolizumab and cisplatin or carboplatin compared with pemetrexed in combination with placebo and cisplatin or carboplatin. It focused on 616 untreated patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression. Patients had no sensitizing EGFR or ALK genomic tumor aberration and had not previously received systemic therapy for advanced disease.
The median overall survival in the pemetrexed/pembrolizumab/platinum chemotherapy arm was not reached versus 11.3 months in the pemetrexed/placebo/platinum chemotherapy arm; the median progression-free survival in the pemetrexed/pembrolizumab/platinum chemotherapy arm was 8.8 months versus 4.9 months in the pemetrexed/placebo/platinum chemotherapy arm. The overall response rate was 48% with pembrolizumab versus 19% without pembrolizumab.
Pemetrexed was discontinued for adverse reactions in 23% of patients who received pemetrexed/pembrolizumab/platinum chemotherapy. The most common adverse reactions resulting in discontinuation of pemetrexed in this arm were acute kidney injury (3%) and pneumonitis (2%).