FDA Approves Adjuvant Pembrolizumab in NSCLC

FDA

The FDA has approved pembrolizumab (Keytruda) as an adjuvant treatment following resection and platinum-based chemotherapy for patients with stage IB (T2a ≥4 cm), II, or IIIA non–small cell lung cancer (NSCLC).¹

The decision was based on findings from the multicenter, randomized, triple-blind, placebo-controlled KEYNOTE-091 trial, (NCT02504372), in which the median investigator-assessed disease-free survival (DFS) was 58.7 months (95% CI, 39.2-not reached [NR]) with pembrolizumab and 34.9 months (95% CI, 28.6-NR) in the placebo arm (HR, 0.73; 95% CI, 0.60-0.89) in patients who received adjuvant chemotherapy.²

In an exploratory subgroup analysis of 167 patients who did not receive adjuvant chemotherapy, the DFS hazard ratio was 1.25 (95% CI, 0.76-2.05).

The recommended dose for pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or up to 1 year.

In KEYNOTE-091, 1177 patients who could not have received neoadjuvant radiotherapy or chemotherapy were randomized 1:1 to receive pembrolizumab at 200 mg or placebo intravenously every 3 weeks for up to 1 year.

Patients were stratified by receipt of adjuvant chemotherapy and region of the world. Of the 1177 patients randomized, 86% had received adjuvant platinum-based chemotherapy following complete resection.

The primary end point was was DFS, and overall survival (OS) was an additional outcome measure.

Among the 1010 patients who received adjuvant platinum-based chemotherapy, the median age was 64 years (range, 35-84), and 49% were age 65 or older. Sixty-eight percent of patients were male, 77% were White, 18% were Asian, and 86% were current or former smokers; 39% of patients with an ECOG performance status of 1.

Patients either had stage IB disease (11%), stage II (57%), or stage IIIA disease (31%). Thirty-nine percent had PD-L1 tumor positive score (TPS) less than 1% [negative], 33% had TPS 1% to 49%, and 28% had TPS 50% or higher. A total 52% of patients were from Western Europe, 20% from Eastern Europe, 17% from Asia, and 11% were from Rest of World.

The OS data were immature at the time of the analysis.

Regarding safety, many of the adverse events that were reported on the KEYNOTE-091 study were similar to other single-agent pembrolizumab studiesobserved in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving KEYTRUDA as a single agent, except for hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two patients died due to myocarditis.

References

1. FDA approves pembrolizumab as adjuvant treatment for non-small cell lung cancer. News release. FDA. January 26, 2023. Accessed January 26, 2023. https://www.fda.gov/drugs

2. Keytruda. Prescribing information. Merck; 2023. Accessed January 26, 2023.