Adjuvant pembrolizumab prolongs disease-free survival (DFS), compared with placebo, in patients with stage IB-IIIA, resected non-small cell lung cancer (NSCLC), according to phase 3 data published in The Lancet Oncology.
There was no improvement in overall survival (OS) with pembrolizumab in this trial, but the data are immature and longer follow-up is needed, according to the researchers.
The trial, PEARLS/KEYNOTE-091 (ClinicalTrials.gov Identifier: NCT02504372), included 1177 patients with completely resected, stage IB-IIIA NSCLC. They were randomly assigned to receive 200 mg of pembrolizumab (n=590) or placebo (n=587), given every 3 weeks for up to 18 cycles.
Adjuvant chemotherapy was strongly recommended for patients with stage II and IIIA disease, and it was allowed in patients with stage IB disease.
The co-primary endpoints were DFS in the overall population and DFS among patients with a PD-L1 tumor proportion score (TPS) of 50% or higher. The median follow-up was 35.6 months.
The median DFS was 53.6 months in the pembrolizumab arm and 42.0 months in the placebo arm (hazard ratio [HR], 0.76; 95% CI, 0.63-0.91; P =.0014). The 24-month DFS rate was 67% with pembrolizumab and 59% with placebo. The 36-month DFS rate was 58% and 50%, respectively.
Among patients with a PD-L1 TPS of 50% or higher, the median DFS was not reached in either arm (HR, 0.82; 95% CI, 0.57-1.18; P =.14). The 24-month DFS rate was 68% with pembrolizumab and 67% with placebo. The 36-month DFS rate was 66% and 58%, respectively.
The median OS was not yet reached in either arm (HR, 0.87; 95% CI, 0.67-1.15; P =.17). The 24-month OS rate was 89% with pembrolizumab and 88% with placebo. The 36-month OS rates were 82% and 80%, respectively.
Grade 3-5 adverse events (AEs) were seen in 34% of patients in the pembrolizumab arm and 26% of patients in the placebo arm. The most common grade 3 or higher AEs in the pembrolizumab arm were hypertension (6%) and pneumonia (2%). Hypertension (6%) and increased body weight (2%) were the most common grade 3 or higher AEs in the placebo arm.
There were 4 treatment-related deaths with pembrolizumab and none with placebo. The deaths related to pembrolizumab were due to cardiogenic shock/myocarditis, septic shock/myocarditis, pneumonia, and sudden death.
Based on these results, the researchers concluded that pembrolizumab “is potentially a new treatment option for stage IB-IIIA NSCLC after complete resection,” in combination with adjuvant chemotherapy when recommended.
Disclosures: This study was supported by Merck Sharp & Dohme. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
O’Brien M, Paz-Ares L, Marreaud S, 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. Published online September 12, 2022. doi:10.1016/S1470-2045(22)00518-6