120MO Adjuvant pembrolizumab versus placebo for early-stage NSCLC after resection and optional chemotherapy: Updated results from PEARLS/KEYNOTE-091

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.