FDA Approves Pembrolizumab With Chemotherapy as First-Line Treatment of Metastatic NSCLC
Posted: Friday, November 2, 2018
On October 30, 2018, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) in combination with carboplatin and either paclitaxel or nab-paclitaxel as first-line treatment of metastatic squamous non–small cell lung cancer (NSCLC).
Approval was based on KEYNOTE-407 (ClinicalTrials.gov identifier NCT02775435), a randomized, multicenter, double-blind, placebo-controlled clinical trial of 559 patients with metastatic squamous NSCLC, regardless of PD-L1 tumor expression status, who had not previously received systemic therapy for metastatic disease. Patients were randomly assigned to pembrolizumab or placebo in combination with carboplatin and investigator’s choice of either paclitaxel every 3 weeks or nab-paclitaxel weekly on a 3-week cycle for 4 cycles followed by pembrolizumab or placebo. Patients continued treatment until disease progression, unacceptable toxicity, or a maximum of 24 months.
The trial demonstrated statistically significant improvements in overall survival, progression-free survival, and overall response rate for patients who received pembrolizumab plus chemotherapy compared with those who received placebo plus chemotherapy. The median overall survival was 15.9 and 11.3 months for the pembrolizumab plus chemotherapy and placebo plus chemotherapy arms, respectively. The median progression-free survival was 6.4 and 4.8 months for the pembrolizumab plus chemotherapy and placebo plus chemotherapy arms, respectively. The overall response rates of the initial 204 patients randomly assigned were 58% and 35%, favoring the pembrolizumab-containing arm. The estimated median response durations were 7.2 and 4.9 months, respectively.
The most common adverse reactions in at least 20% of patients who received pembrolizumab in KEYNOTE-407 were fatigue/asthenia, nausea, constipation, diarrhea, vomiting, pyrexia, decreased appetite, rash, cough, dyspnea, alopecia, and peripheral neuropathy.
