Adjuvant pembrolizumab can prolong disease-free survival (DFS) after surgical resection in patients with early stage non-small cell lung cancer (NSCLC), according to results of the phase 3 PEARLS/KEYNOTE-091 study.

Pembrolizumab prolonged DFS, when compared with placebo, in the overall patient population, but there was no DFS improvement among patients with high PD-L1 expression.

“Overall, we believe that pembrolizumab has the potential to become a new adjuvant treatment option for patients with stage IB of more than 4 cm, stage II, and stage IIIA NSCLC following complete resection and adjuvant chemotherapy when recommended, regardless [of] PD-L1 expression,” said Luis Paz-Ares, MD, PhD, of the Hospital Universitario 12 de Octubre in Madrid, Spain.

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Dr Paz-Ares outlined these results from KEYNOTE-091 in an ESMO Virtual Plenary presentation.

The KEYNOTE-091 trial ( identifier: NCT02504372) was designed to compare pembrolizumab and placebo in patients with stage IB-IIIA NSCLC who had undergone surgical resection with or without adjuvant chemotherapy.

The trial included 1177 patients. They were randomly assigned to receive pembrolizumab (n=590) or placebo (n=587) every 3 weeks for up to 18 doses over approximately 1 year.

The dual primary endpoints were DFS in the overall population and in the subgroup of patients with high PD-L1 expression, defined as a tumor proportion score (TPS) of 50% or greater. A similar proportion of patients in the pembrolizumab and placebo arms had high PD-L1 expression (28.5% and 28.1%, respectively).


At a median follow-up of 35.6 months, the median DFS was 53.6 months with pembrolizumab and 42.0 months with placebo, a difference that was statistically significant (hazard ratio [HR], 0.76; 95% CI, 0.63-0.91; P =.0014). The 18-month DFS rate was 73.4% in the pembrolizumab arm and 64.3% in the placebo arm.

Dr Paz-Ares noted that there was a DFS benefit with pembrolizumab across most subgroups. However, there was no significant difference in DFS between the treatment arms for patients with high PD-L1 expression.

Among patients with a PD-L1 TPS of 50% or greater, the median DFS was not reached in either treatment arm. The 18-month DFS rate was 71.7% in the pembrolizumab arm and 70.2% in the placebo arm (HR, 0.82; 95% CI, 0.57-1.18; P =.14).

Dr Paz-Ares said the overall survival (OS) data are immature, and findings did not reach statistical significance at the time of the interim analysis. The 18-month OS rate was 91.7% with pembrolizumab and 91.3% with placebo (HR, 0.87; 95% CI, 0.67-1.15; P =.17).

Grade 3 to 5 adverse events (AEs) were observed more frequently in the pembrolizumab arm (34.1%) than in the placebo arm (25.8%). Serious AEs occurred in 24.5% and 15.5% of patients, respectively.

There were 4 treatment-related deaths in the pembrolizumab arm and none in the placebo arm. The 4 deaths were due to pneumonia, sudden death, myocarditis plus cardiogenic shock, and myocarditis plus septic shock.

Disclosures: This research was supported by Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Paz-Ares L, O’Brien MER, Mauer M, et al. Pembrolizumab (pembro) versus placebo for early-stage non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy (chemo) when indicated: Randomized, triple-blind, phase III EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study. Presented at 2022 ESMO Virtual Plenary Series; March 17, 2022. Abstract VP3-2022.