Frontline Dostarlimab/Chemo Maintains Numerical OS Benefit in Advanced NSCLC

The combination of dostarlimab-gxly (Jemperli) and chemotherapy maintained a numerical improvement in overall survival (OS) compared with pembrolizumab (Keytruda) plus chemotherapy in the first-line treatment of patients with advanced non–small cell lung cancer (NSCLC), according to updated findings from the phase 2 PERLA trial (NCT04581824) presented at the 2024 SITC Annual Meeting.

In the dostarlimab arm, the median duration of follow-up was 31.1 months (95% CI, 29.9-33.8) vs 31.9 months (95% CI, 30.7-33.1) in the pembrolizumab arm. The median overall survival (OS) in the dostarlimab arm was 20.2 months (95% CI, 14.5-27.3) vs 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 arm 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.

OS results were also stratified by PD-L1 status. For those with a PD-L1 tumor proportion score (TPS) of less than 1%, the median OS was 20.8 months (95% CI, 11.4-not reached [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). For those with a PD-L1 TPS of 1% to 49%, the median OS was 17.1 months (95% CI, 9.5-27.3) vs 14.5 months (95% CI, 6.5-NR). Finally, for patients with a PD-L1 TPS of 50% or more, the median OS was NR (95% CI, 9.9-NR) vs 17.6 (95% CI, 6.2-32.3).

“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,” Solange Peters, MD, PhD, noted during the presentation. “The previously observed numerical trend in OS favoring dostarlimab plus chemotherapy vs pembrolizumab and chemotherapy was maintained.”

Peters is a 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 PERLA trial assessed 243 patients who were randomly assigned 1:1 to 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 weeks 9 to 48, followed by every 12 weeks thereafter.

The primary end point was objective response rate by RECIST v1.1 criteria confirmed by blinded independent central review. Secondary end points were OS, progression-free survival, and safety.

A majority of patients between the dostarlimab and pembrolizumab arms were male (70% vs 63%), and the median age was 64.0 years vs 65.0 years. Brain metastases were present (18% vs 12%), and an ECOG performance status of 1 was noted in each arm (69% vs 59%).

Additionally, the most common patient ethnicity was Other (74% vs 69%) followed by Hispanic or Latino (21% vs 26%). The most common race was White (72% vs 69%), and most patients were enrolled in Europe (51% vs 53%).

Overall, 36% of patients in the dostarlimab arm and 21% in the pembrolizumab arm are still receiving treatment, while 64% vs 79% have completed therapy. Of note, 61% vs 73% of patients died due to any reason, and 2% vs 6% of patients withdrew from the study.

The safety profile remained consistent with previous results. Any-grade adverse effects (AEs) were noted in 98% of patients in the dostarlimab arm vs 98% in the pembrolizumab arm. In each arm, 85% vs 81% had treatment-related AEs, and 65% vs 66% had AEs that were grade 3 or higher. Fatal AEs occurred in 12% vs 10% of patients, respectively.

Reference

Peters S, Lim SM, Ortega G, et al. Updated overall survival from PERLA a phase II randomized double-blind trial of dostarlimab + chemotherapy vs pembrolizumab + chemotherapy in metastatic non-squamous non-small cell lung cancer. Presented at the 2024 Society for Immunotherapy of Cancer Annual Meeting; November 6-10, 2024; Houston, TX. Abstract 711.