Progression-free survival was increased in patients with primary advanced or recurrent endometrial cancer — particularly those with mismatch repair–deficient (dMMR), microsatellite instability–high (MSI-H) tumors — when treated with dostarlimab plus carboplatin–paclitaxel. The authors caution: “The progression-free survival benefit in the dostarlimab group did not appear to be consistent across all prespecified subgroups; extended follow-up may be necessary in order to observe a treatment effect in the subgroup of patients with stage III disease and the subgroup of patients with no disease at baseline because of the limited sample size and the relatively short follow-up period.”
In a phase 3, global, double-blind, randomized, placebo-controlled trial, patients with primary advanced stage III or IV or first recurrent endometrial cancer randomly received either dostarlimab 500 mg or placebo, plus carboplatin and paclitaxel, every 3 weeks (6 cycles), followed by dostarlimab 1000 mg or placebo every 6 weeks for up to 3 years.
Based on primary endpoints of progression-free survival, the study found: “Of the 494 patients who underwent randomization, 118 (23.9%) had [dMMR–MSI-H] tumors. In the dMMR–MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval [CI], 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P <0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P <0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group.”