FDA grants regular approval to Keytruda-chemotherapy combination for nonsquamous non-small cell lung cancer

The FDA granted regular approval to pembrolizumab in combination with pemetrexed and platinum-based chemotherapy as first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer.

The approval applies to patients who do not harbor EGFR or ALK genomic tumor aberrations.

Pembrolizumab (Keytruda, Merck) is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

The FDA had granted accelerated approval for this indication in May 2017 based on the results of the open-label, multicenter KEYNOTE-021 trial.

The trial compared first-line pembrolizumab plus pemetrexed (Alimta, Eli Lilly) and carboplatin with pemetrexed and carboplatin alone for 123 treatment-naive patients with metastatic nonsquamous NSCLC. The patients had no EGFR or ALK genomic tumor aberrations, and they received treatment irrespective of PD-L1 expression.

Results showed the addition of pembrolizumab extended median PFS (13 months vs. 8.9 months; HR = 0.53; 0.31-0.91) and improved objective response rate (55% vs. 29%).

The FDA based regular approval on results from the randomized, multicenter, double-blind KEYNOTE-189 trial.

The analysis included 616 patients with previously untreated nonsquamous NSCLC. Researchers randomly assigned patients 2:1 to pembrolizumab or placebo in combination with pemetrexed and investigator’s choice of either cisplatin or carboplatin every 3 weeks for four cycles, followed by pembrolizumab or placebo and pemetrexed.

Treatment continued for up to 24 months, or until disease progression or unacceptable toxicity.

OS and PFS served as primary endpoints.

Patients assigned pembrolizumab plus chemotherapy achieved superior OS (HR = 0.49; 95% CI, 0.38-0.64), according to results of a prespecified interim analysis.

At data cutoff, median OS had not been reached for those assigned pembrolizumab plus chemotherapy, and it was 11.3 months for those assigned placebo plus chemotherapy.

Median PFS was 8.8 months for patients assigned pembrolizumab plus chemotherapy, compared with 4.9 months for those who received placebo plus chemotherapy (HR = 0.52; 95% CI, 0.43-0.64).

Researchers also reported a higher overall response rate (48% vs. 19%; P = .0001) and longer median duration of response (11.2 months vs. 7.8 months) among pembrolizumab-treated patients.

The most common adverse reactions that occurred in at least 20% of patients included fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea and pyrexia.