The Food and Drug Administration has granted accelerated approval to checkpoint inhibitor pembrolizumab in combination with pemetrexed and carboplatin for the treatment of patients with previously untreated metastatic nonsquamous non–small cell lung cancer (NSCLC).
The immunotherapy pembrolizumab was approved as a second-line treatment for metastatic NSCLC in 2015.
First-line approval was based on an improved overall response rate (ORR) and progression-free survival (PFS) in a cohort of 123 patients within an open-label, multicohort study (KEYNOTE-21). Enrollees in cohort G1 had locally advanced or metastatic NSCLC and no prior systemic treatment for metastatic disease. They were randomized to receive either pembrolizumab, in combination with pemetrexed and carboplatin (PC) for four cycles followed by pembrolizumab for a maximum of 24 months (n = 60) or PC alone (n = 63). Randomization was stratified by PD-L1 tumor expression (tumor proportion score [TPS] less than 1% vs. TPS greater than or equal to 1%).
The hazard ratio for PFS was 0.53 (95% CI: 0.31, 0.91, P = .0205). The median PFS was 13.0 months for the pembrolizumab plus PC arm and 8.9 months for the PC-alone arm. In the TPS less than 1% subgroup, the ORR was 57% and 13% in the pembrolizumab-plus-PC and in the PC-alone arms, respectively. In the TPS greater-than-or-equal-to-1% subgroup, the ORR was 54% in the pembrolizumab-plus-PC arm and 38% in the pembrolizumab-plus-PC arm, the FDA said.
There were serious adverse events in 41% of the patients in the pembrolizumab-plus-PC arm compared with 28% in the PC-alone arm. Pembrolizumab was discontinued for adverse reactions in 10% of patients, most commonly due to acute kidney injury. The most common grade 3-4 adverse reactions were fatigue, dyspnea, nausea, vomiting, diarrhea, and rash.
The FDA cautioned that immune-mediated adverse reactions can occur with pembrolizumab including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based on the severity of the adverse reaction, pembrolizumab should be withheld or discontinued and corticosteroids administered when appropriate. The recommended dose and schedule for NSCLC is 200 mg as an intravenous infusion every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab is marketed as Keytruda by Merck.