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.

Results

At the end of the study (September 10, 2024), the median follow-up time (mo) for PFS was 30.4 for D+CT and 30.4 for P+CT. The median PFS (mo [95% confidence interval (CI)]) was 8.8 (6.9–11.0) for D+CT and 6.8 (4.9–7.1) for P+CT (hazard ratio 0.77 [95% CI: 0.58–1.03] at 79% maturity). The median follow-up time (mo) for OS 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.