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

Abstract

VP3-2022: 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

Published: March 17, 2022
DOI: https://doi.org/10.1016/j.annonc.2022.02.224
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L. Paz-Ares; M.E.R. O'Brien; M. Mauer; R.A. Stahel; S. Peters; B. Besse
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Background

Pembro is a standard of care for advanced NSCLC. PEARLS/KEYNOTE-091 (NCT02504372) evaluated adjuvant pembro vs placebo for patients (pts) with completely resected early-stage NSCLC.

Methods

Eligible pts with completely resected stage IB (T ≥4 cm), II, or IIIA NSCLC per AJCC v7 followed by adjuvant chemo as indicated per guidelines, ECOG PS 0-1, and any PD-L1 expression were randomized 1:1 to pembro 200 mg or placebo Q3W for 18 doses (~1 year). Dual primary end points are DFS in the all-comers and PD-L1 TPS ≥50% populations. Secondary end points are DFS in the TPS ≥1% population, OS in the all-comers, TPS ≥50% and ≥1% populations, and safety. Data are from the protocol-specified second interim analysis (IA2; 20 September 2021, data cutoff).

Results

1177 pts were randomized to pembro (N = 590) or placebo (N = 587), including 168 and 165, respectively, who had TPS ≥50%. Baseline characteristics were generally balanced between arms. Median time from randomization to data cutoff for IA2 was 35.6 mo (range 16.5-68.0). DFS was significantly improved with pembro in the all-comers population (median 53.6 vs 42.0 mo; HR 0.76; 95% CI 0.63-0.91; P = 0.0014); the significance boundary was not crossed for the TPS ≥50% population (median not reached in either arm; HR 0.82; 95% CI 0.57-1.18; P = 0.14). With only 209 events, the significance boundary for OS in the all-comers population was not crossed (18-mo rate 91.7% vs 91.3%; HR 0.87; 95% CI 0.67-1.15; P = 0.17). Median number of doses was 17 for pembro vs 18 for placebo. AEs were grade ≥3 in 34.1% of pts in the pembro arm vs 25.8% in the placebo arm and led to discontinuation in 19.8% vs 5.9%; treatment-related AEs led to death in 0.7% vs 0%.

Conclusions

Adjuvant pembro provided a statistically significant, clinically meaningful DFS improvement following complete resection and, when indicated, adjuvant chemo in pts with stage IB (T ≥4 cm)-IIIA NSCLC, regardless of PD-L1 expression. The pembro safety profile was as expected. DFS in the PD-L1-defined populations and OS will be tested at future analyses according to the analysis plan.

Clinical trial identification

NCT02504372, first posted 21 July 2015.