Updated findings from the phase 2 PERLA trial, presented at the 2024 SITC Annual Meeting, reveal that the combination of dostarlimab-gxly (Jemperli) and chemotherapy continues to demonstrate a numerical improvement in overall survival (OS) compared to pembrolizumab (Keytruda) plus chemotherapy as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The study's results suggest a potential advantage for dostarlimab in this setting, warranting further investigation.
Sustained Overall Survival Benefit
With a median follow-up of 31.1 months (95% CI, 29.9-33.8) in the dostarlimab arm and 31.9 months (95% CI, 30.7-33.1) in the pembrolizumab arm, the median overall survival (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, with a hazard ratio of 0.74 (95% CI, 0.54-1.00). These results indicate a clinically meaningful trend favoring dostarlimab, although the confidence interval includes 1.
The OS rates at various time points further highlight this trend. At 12 months, the OS rates were 63% in the dostarlimab arm and 58% in the pembrolizumab arm. These rates shifted to 51% vs 43% at 18 months, 46% vs 33% at 24 months, and 40% vs 27% at 30 months, respectively, demonstrating a sustained benefit over time.
Impact of PD-L1 Expression
OS results were also stratified by PD-L1 tumor proportion score (TPS). In 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 compared to 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), respectively. These findings suggest that the survival benefit of dostarlimab may extend across different levels of PD-L1 expression.
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," noted Solange Peters, MD, PhD, a full professor and chair of Medical Oncology and Thoracic Malignancies Programmae 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."
Trial Design and Patient Characteristics
The PERLA trial involved 243 patients randomly assigned (1:1) to receive either dostarlimab at 500 mg intravenously plus chemotherapy every 3 weeks (n = 121) or pembrolizumab at 200 mg intravenously plus chemotherapy every 3 weeks (n = 122). Disease was assessed via clinic visits every 3 weeks, with serial imaging completed at weeks 6 and 12, then every 9 to 48 weeks, followed by every 12 weeks thereafter.
The primary endpoint was objective response rate (ORR) by RECIST v1.1 criteria confirmed by blinded independent central review. Secondary endpoints included OS, progression-free survival (PFS), and safety.
Patient demographics were generally balanced between the two arms. The majority of patients were male (70% in the dostarlimab arm vs 63% in the pembrolizumab arm), with median ages of 64.0 and 65.0 years, respectively. Brain metastases were present in 18% and 12% of patients, respectively, and an ECOG performance status of 1 was noted in 69% and 59% of patients, respectively.
Safety Profile
The safety profile remained consistent with previous results. Any-grade adverse events (AEs) were reported in 98% of patients in both the dostarlimab and pembrolizumab arms. Treatment-related AEs occurred in 85% vs 81% of patients, respectively, and grade 3 or higher AEs were observed in 65% vs 66% of patients, respectively. Fatal AEs occurred in 12% vs 10% of patients, respectively.
