On January 26, 2023, the FDA approved pembrolizumab (Keytruda; Merck), a PD-1 inhibitor, as monotherapy for adjuvant treatment of patients with stage IB (T2a ≥4 cm), II, or IIIA non–small-cell lung cancer (NSCLC), after resection and platinum-based chemotherapy.
Pembrolizumab monotherapy was previously approved for the first-line treatment of patients with NSCLC and PD-L1 expression but without ALK or EGFR mutations, and for patients with metastatic NSCLC and PD-L1 expression, following platinum-based chemotherapy.
The FDA approval of pembrolizumab as monotherapy for adjuvant treatment of patients with NSCLC was based on the results of the multicenter, randomized, triple-blind, placebo-controlled KEYNOTE-091 clinical trial of patients who had not received neoadjuvant radiotherapy or chemotherapy. The patients were randomized (1:1) to adjuvant treatment with pembrolizumab 200 mg or to placebo intravenously every 3 weeks for up to 1 year. Of the 1177 patients in the study, 1010 (86%) patients received adjuvant platinum-based chemotherapy after complete resection.
The main end point was disease-free survival (DFS). The results showed a significant improvement in DFS with pembrolizumab versus placebo in the overall population. Among patients who received adjuvant chemotherapy, the median DFS was 58.7 months in the pembrolizumab arm (95% confidence interval [CI], 39.2-not reached) versus 34.9 months in the placebo arm (95% CI, 28.6-not reached; hazard ratio [HR], 0.73; 95% CI, 0.60-0.89). In a subgroup analysis of 167 patients who did not receive adjuvant chemotherapy, the HR for DFS was 1.25 (95% CI, 0.76-2.05).
The adverse events in KEYNOTE-091 were similar to those seen with pembrolizumab monotherapy in patients with NSCLC, with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). In addition, myocarditis led to 2 deaths.