Results from the phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial demonstrated that dostarlimab plus carboplatin and paclitaxel followed by dostarlimab and niraparib significantly improved progression-free survival (PFS) among patients with primary advanced or recurrent endometrial cancer, regardless of mismatch repair proficient/microsatellite stable (MMRp/MSS) status.

Mansoor R. Mirza, MD, Copenhagen University Hospital, Denmark, presented these results at the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women's Cancers in San Diego, California. 

As previously reported in part 1 of this study, "patients receiving dostarlimab [plus] carboplatin [and] paclitaxel exhibited significant benefits in PFS and overall survival versus carboplatin [and] paclitaxel alone," stated Dr Mirza and coauthors. "There remains an unmet need for treatment options for patients with [primary advanced or recurrent endometrial cancer]...which may be met by combining immunotherapy with a poly ADP-ribose polymerase inhibitor."

In this part 2 analysis, 291 patients with primary advanced or recurrent endometrial cancer were randomized on a 2-to-1 basis to receive either 500 mg of dostarlimab plus carboplatin and paclitaxel once every 3 weeks for 6 cycles followed by 1000 mg of dostarlimab once every 6 weeks plus niraparib (at an individualized starting dose based on baseline body weight and platelet count) once daily for ≤ 3 years (n = 192) or placebo plus carboplatin and paclitaxel once every 3 weeks for 6 cycles followed by placebo for ≤ 3 years (n = 99). The primary end point was investigator-assessed PFS in both the overall and the MMRp/MSS populations (n = 216).

At a median follow-up of 19 months, PFS was 14.5 months in the dostarlimab arm and 8.3 months in the placebo arm (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.43 to 0.82; P = .0007). In the MMRp/MSS population, PFS was 14.3 months in the dostarlimab arm and 8.3 months in the placebo arm (HR, 0.63; 95% CI, 0.44 to 0.91; P = .0060). Grade  ≥ 3 treatment-emergent adverse events were reported by 84% of patients in the dostarlimab arm and 49% of patients in the placebo arm. The most frequent events included nausea, fatigue, and anemia. In the dostarlimab arm, there were 4 deaths due to treatment-emergent adverse events deemed unrelated to the treatment regimen.

Dr Mirza et al concluded "dostarlimab [plus] carboplatin [and] paclitaxel, followed by dostarlimab and niraparib, is an effective and safe combination therapy for [primary advanced or recurrent endometrial cancer] ...demonstrating a potential role for PARP inhibition in this setting."

Source: 

Mirza MR, Ghamande S, Hanker LC, et al. Dostarlimab plus chemotherapy followed by dostarlimab plus niraparib maintenance therapy in patients with primary-advanced or recurrent endometrial cancer in the ENGOT-EN6-NSGO/GOG-3031/RUBY Trial. Presented at the SGO 2024 Annual Meeting; March 16-18, 2024. San Diego, California