PEARLS/KEYNOTE-091: Adjuvant Pembrolizumab in Completely Resected Stage IB–IIIA NSCLC

By: Victoria Kuhr, BA
Posted: Tuesday, January 10, 2023

In a phase III triple-blind trial (PEARLS/KEYNOTE-091), the PD-1 inhibitor pembrolizumab significantly improved disease-free survival compared with placebo in patients with PD-L1–unselected, stage IB–IIIA non–small cell lung cancer (NSCLC). Additionally, Mary O’Brien, MD, of Royal Marsden Hospital, London, and colleagues reported that pembrolizumab was not associated with new safety signals. These findings were published in The Lancet Oncology.

“The absence of a disease-free survival benefit for pembrolizumab in the PD-L1 [tumor proportion score (TPS)] of 50% or greater population at the time of this interim analysis was unexpected,” said the study authors. “The relative benefit of pembrolizumab monotherapy increases with increasing PD-L1 expression in the setting of locally advanced or metastatic NSCLC.”

The study included patients with completely resected, pathologically confirmed stage IB, II, or IIIA NSCLC, based on the American Joint Committee on Cancer staging system. Patients were recruited from 196 medical centers in 29 countries between January 2016 and May 2020. The data cutoff was September 2021.

A total of 1,177 participants were included in the study. Of them, 590 participants received pembrolizumab (including 168 with a PD-L1 TPS of more than 50%), and 587 participants received the placebo (including 168 with a PD-L1 TPS of more than 50%). The median follow-up was 35.6 months. The median disease-free survival was 53.6 months with pembrolizumab versus 42 months with the placebo. Of patients with a PD-L1 TPS of more than 50%, the median disease-free survival was not reached in either group.

Adverse events of grade 3 or higher were reported in 198 of 580 participants (34%) who received pembrolizumab and in 150 of 581 participants (26%) who received placebo. Grade 3 or higher events included hypertension and pneumonia in both groups. There were four treatment-related adverse events that led to death.

Disclosure: For full disclosures of the study authors, visit www.thelancet.com.

The Lancet Oncology

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