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 e PEARLS/KEYNOTE-091 study

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 (w1 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, clini-cally 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.

Automated summary

This study evaluated the efficacy of adjuvant pembrolizumab compared to placebo in patients with completely resected early-stage non-small cell lung cancer. The results showed that adjuvant pembrolizumab significantly improved disease-free survival in the overall population, but did not reach statistical significance in the PD-L1 expression >= 50% population. Adverse events were more common in the pembrolizumab group compared to the placebo group.