Updated results from the phase 2 PERLA trial indicate that dostarlimab-gxly (Jemperli) combined with chemotherapy shows promising clinical efficacy compared to pembrolizumab (Keytruda) plus chemotherapy as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The findings, presented at the 2024 Society for Immunotherapy of Cancer Annual Meeting, highlight a potential survival benefit with the dostarlimab regimen.
The PERLA trial randomly assigned 243 patients to either dostarlimab (500 mg intravenously every 3 weeks) plus chemotherapy (n = 121) or pembrolizumab (200 mg intravenously every 3 weeks) plus chemotherapy (n = 122). The primary endpoint was objective response rate. Secondary endpoints included overall survival (OS), progression-free survival, and safety.
Overall Survival Benefit
With a median follow-up of 31.1 months in the dostarlimab arm and 31.9 months in the pembrolizumab arm, the median OS was 20.2 months (95% CI, 14.5-27.3) in the dostarlimab arm compared to 15.9 months (95% CI, 11.6-19.3) in the pembrolizumab arm (HR, 0.74; 95% CI, 0.54-1.00). The OS rates for the dostarlimab and pembrolizumab arms were 63% vs 58% at 12 months, 51% vs 43% at 18 months, 46% vs 33% at 24 months, and 40% vs 27% at 30 months.
PD-L1 Status and Survival
OS results were stratified by PD-L1 tumor proportion score (TPS). For patients with a PD-L1 TPS of less than 1%, the median OS was 20.8 months (95% CI, 11.4-NR) in the dostarlimab arm vs 16.1 months (95% CI, 11.5-20.1) in the pembrolizumab arm. For those with a PD-L1 TPS of 1% or more, the median OS was 19.4 months (95% CI, 10.6-31.2) vs 15.9 months (95% CI, 7.8-22.2).
Safety Profile
The safety profile remained consistent with previous results. Any-grade adverse effects (AEs) were noted in 98% of patients in both arms. Treatment-related AEs occurred in 85% of patients in the dostarlimab arm and 81% in the pembrolizumab arm, with grade 3 or higher AEs in 65% vs 66%, respectively. Fatal AEs occurred in 12% vs 10% of patients.
Expert Commentary
"The updated OS analysis reaffirms the previous observation that efficacy and safety data were generally comparable between patients with dostarlimab plus chemotherapy and those treated with pembrolizumab plus chemotherapy," said Solange Peters, MD, PhD, full professor and chair of Medical Oncology and Thoracic Malignancies Programmae in the Department of Oncology at the University Hospital of Lausanne in Switzerland. "The previously observed numerical trend in OS favoring dostarlimab plus chemotherapy vs pembrolizumab and chemotherapy was maintained."
