Long-term Survival Analysis From PERLA, A Phase II Randomized Trial of Dostarlimab With Chemotherapy Versus Pembrolizumab With Chemotherapy in Metastatic Nonsquamous NSCLC

Abstract

Introduction: PERLA is a global, double-blind, phase II trial comparing anti-programmed cell death protein 1 antibodies, dostarlimab, and pembrolizumab in combination with chemotherapy (D+CT and P+CT, respectively) in patients with metastatic nonsquamous NSCLC without actionable genomic aberrations in the first-line setting. Methods: Patients were randomized 1:1 to receive not more than 35 cycles of 500 mg dostarlimab or 200 mg pembrolizumab, with less than or equal to 35 cycles of 500 mg/m2 pemetrexed and less than or equal to 4 cycles of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg/mL/min) every 3 weeks. The primary end point was the overall response rate by blinded independent central review. The secondary end points included progression-free survival (PFS) on the basis of investigator assessment, overall survival (OS), and safety. Here, we reported on the long-term OS, PFS, and safety analyses. was 35.5 for D+CT and 35.2 for P+CT. The median OS (mo [95% CI]) was 20.2 (14.5-27.3) and 15.9 (11.6-19.3), respectively (hazard ratio 0.75 [95% CI: 0.55-1.02] at 70% maturity). Safety profiles were similar between arms and consistent with previous analyses. Conclusions: This long-term analysis reaffirms previous observations that D+CT exhibited similar efficacy to P+CT and exhibits strong clinical efficacy as a first-line treatment for patients with metastatic nonsquamous NSCLC. Clinical trial registration: NCT04581824. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).