120MO Adjuvant pembrolizumab versus placebo for early-stage NSCLC after resection and optional chemotherapy: Updated results from PEARLS/KEYNOTE-091
Benjamin Besse, Libor Havel, Solange Peters, Sandrine Marréaud, Nitish Jha, Kersti Oselin, E. Esteban Gonzalez, M.D. Isla Casado, Alex Martínez‐Martí, Martin Faehling, JS Lee, Yun Luo, S.M. Keller, Urania Dafni, M. Mauer, R.A. Stahel, E O’Brien, Masahiro Tsuboi, L. Paz-Ares
Abstract
At second interim analysis (IA2) of the phase 3 PEARLS/KEYNOTE-091 study of completely resected stage IB–IIIA NSCLC per AJCC v7 (NCT02504372), pembrolizumab (pembro) as adjuvant therapy significantly improved DFS vs placebo (pbo) in the ITT population (HR, 0.76; 95% CI, 0.63–0.91; P = 0.0014); significance was not achieved in the PD-L1 TPS ≥50% population (0.82; 95% CI, 0.57–1.18; P = 0.14). We report results from IA3, the final DFS analysis. Eligible pts aged ≥18 y with completely resected stage IB (T ≥4 cm), II, or IIIA NSCLC (AJCC v7), ECOG PS 0 or 1, and tumor sample for PD-L1 testing received optional adjuvant chemotherapy (chemo) for ≤4 cycles as indicated per guidelines. Pts were randomized 1:1 to pembro 200 mg or pbo Q3W for 18 doses (∼1 y). Dual primary endpoints were DFS in the ITT and PD-L1 TPS ≥50% populations. Alpha was assigned to the PD-L1 TPS ≥50% population only (α = 0.0125; significance boundary, P = 0.01038). Of 1177 pts in the ITT population, 590 were randomized to pembro and 587 to pbo. Median follow-up at data cutoff (Jan 24, 2023) was 51.7 (range, 32.7–84.2) mo. DFS was not significantly improved with pembro vs pbo in the PD-L1 TPS ≥50% population (HR, 0.83; 95% CI, 0.59–1.16; P = 0.13); 4y DFS rates (95% CI) were 57.0% (47.9%–65.1%) vs 49.1% (39.8%–57.8%). Outcomes in the ITT and adjuvant chemo populations were generally consistent to IA2 (Table). 198 pts (34.1%) in the pembro group and 150 (25.8%) in pbo group experienced grade ≥3 all-cause AEs; 11 (1.9%) and 6 (1.0%), respectively, had grade 5 AE. 227 (39.1%) and 76 pts (13.1%), respectively, experienced immune-mediated AEs and infusion reactions.Table 120MOPopulationTreatment groupMedian DFS (95% CI), moDFS HR (95% CI)PD-L1 TPS ≥50%Pembrolizumab (n = 168)67.0 (47.8–NR)0.83 (0.59–1.16)Placebo (n = 165)47.6 (36.4–NR)ITTPembrolizumab (n = 590)53.8 (46.2–67.0)0.81 (0.68–0.96)Placebo (n = 587)43.0 (35.0–51.6)Patients who received adjuvant chemotherapyPembrolizumab (n = 506)53.8 (46.2–70.4)0.80 (0.67–0.96)Placebo (n = 504)40.5 (32.9–47.4) Open table in a new tab In this final DFS analysis, adjuvant pembro continued to improve DFS vs pbo in the ITT population, without significant improvement in pts with PD-L1 TPS ≥50%, in stage IB-IIIA NSCLC following complete resection and adjuvant chemo when indicated. Adjuvant pembro has manageable safety, supporting its use in this setting.