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 ( 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.

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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