FDA Approves Pembrolizumab Plus Chemotherapy as First-Line Treatment of NSCLC
Posted: Wednesday, August 22, 2018
On August 20, 2018, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) in combination with pemetrexed and platinum as a first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
This approval is based on the results of KEYNOTE-189 (ClinicalTrials.gov identifier NCT02578680), a randomized, multicenter, double-blind, active controlled study enrolling 616 patients receiving first-line treatment of metastatic nonsquamous NSCLC. Patients were randomized to receive either pembrolizumab or placebo in combination with pemetrexed and investigator’s choice of either cisplatin or carboplatin every 3 weeks for 4 cycles followed by pembrolizumab or placebo and pemetrexed. Treatment with pembrolizumab continued until disease progression, unacceptable toxicity, or a maximum of 24 months.
The trial demonstrated a statistically significant improvement in overall survival for patients treated with pembrolizumab and chemotherapy in a prespecified interim analysis. The median overall survival was not reached at the time of the data cutoff in the pembrolizumab plus chemotherapy arm and was 11.3 months in the chemotherapy-alone arm. The trial also showed improvement in progression-free survival for patients treated with pembrolizumab plus chemotherapy. The median progression-free survival was 8.8 months for patients receiving pembrolizumab plus chemotherapy and 4.9 months for those receiving chemotherapy alone.
The overall response rate was significantly higher for those in the pembrolizumab plus chemotherapy arm (48% vs. 19%), and the median response duration was 11.2 months and 7.8 months, respectively. The most common adverse reactions reported in at least 20% of patients in KEYNOTE-189 were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia.