Poly(adenosine diphosphate-ribose) polymerase inhibitor maintenance therapy with niraparib in patients with primary advanced or recurrent endometrial cancer receiving dostarlimab plus chemotherapy

Objective: Dostarlimab+carboplatin-paclitaxel followed by dostarlimab maintenance demonstrated statistically significant and clinically meaningful benefits in progression-free and overall survival in the overall population of primary advanced/recurrent endometrial cancer versus chemotherapy alone in Part 1 of the phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial (NCT03981796). Part 2 evaluated the efficacy and safety of the addition of the poly(adenosine diphosphate-ribose) polymerase inhibitor niraparib to dostarlimab maintenance following dostarlimab+chemotherapy versus placebo maintenance following placebo+chemotherapy in primary advanced/recurrent endometrial cancer. Methods: Patients were randomized 2:1 to dostarlimab+chemotherapy followed by niraparib+dostarlimab maintenance (niraparib+dostarlimab arm) or placebo+chemotherapy followed by placebo maintenance (control arm). Primary endpoint was progression-free survival in the overall and mismatch repair-proficient/micro-satellite stable populations. Overall survival (key secondary endpoint) and safety were assessed. Results: In total, 291 patients were randomized (192 to niraparib+dostarlimab; 99 to control). With approximately 22 months of follow-up, the risk of progression or death was significantly reduced by 40% (hazard ratio 0.60, 95% confidence interval 0.43 to 0.82, p <.001) and 37% (hazard ratio 0.63, 95% confidence interval 0.44 to 0.91, p =.006) with niraparib+dostarlimab versus the control in the overall and mismatch repair-proficient/micro-satellite stable populations, respectively. At 36.2 months of follow-up, no overall survival benefit was observed with niraparib+dostarlimab versus the control (hazard ratio 1.2, 95% confidence interval 0.81 to 1.78).Grade ≥3 treatment-related adverse events occurred in 70.7% of patients in the niraparib+dostarlimab arm and 37.5% in the control arm; serious treatment-related adverse events occurred in 24.6% and 9.4%, respectively. Discontinuations due to adverse events occurred in 38.7% of patients in the niraparib+dostarlimab arm and 11.5% in the control arm. Conclusions: While the addition of niraparib to dostarlimab maintenance showed a significant improvement in progression-free survival, there was no observed overall survival benefit. Dostarlimab+carboplatin-paclitaxel followed by dostarlimab maintenance remains the only regimen to demonstrate significant overall survival benefit versus carboplatin-paclitaxel alone in primary advanced/recurrent endometrial cancer.