On January 26, 2023, the U.S. Food and Drug Administration approved Pembrolizumab for patients with resectable, stage IB (≥4cm)-IIIA (as per the AJCC 7th Edition Staging System) non-small cell lung cancer after having a complete surgical resection and platinum-based adjuvant chemotherapy .
Study ID number: NCT02504372
The approval was based on the KEYNOTE-091 study, also known as the PEARLS study, a multicenter, triple-blind, randomized, phase 3 study . In this study, 1177 patients were randomized (1:1) to receive pembrolizumab or saline placebo every three weeks for up to 1 year. Adjuvant chemotherapy was not mandatory, but most patients (86%) received adjuvant chemotherapy.
The study had two primary endpoints: disease-free survival (DFS) in the overall population for PD-L1 TPS of 50% or more. The study demonstrated statistically significant improvement in DFS in the overall population: median DFS was 53·6 months (95% CI 39·2 to not reached) versus 42·0 months (31·3 to not reached) in the pembrolizumab and placebo arm respectively. For PD-L1 TPS ≥50%, median DFS was not reached in either arm. OS survival data is immature at the time of data reporting.
There were no new safety signals, and overall, adjuvant pembrolizumab was well tolerated with a side effect profile similar to that of single-agent pembrolizumab used in other cancer treatments. Of note, two cases of fatal (Grade 5) myocarditis were reported in the pembrolizumab arm.
1. FDA approves pembrolizumab as adjuvant treatment for non-small cell lung cancer. Accessed January 26, 2023. https://bit.ly/3HzHHxL
2. O’Brien M et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022 Oct;23(10):1274-1286.