Dostarlimab in primary advanced or recurrent endometrial cancer

Results of the RUBY trial, recently published in The New England Journal of Medicine, show that the immune checkpoint inhibitor dostarlimab plus carboplatin-paclitaxel significantly increases progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in mismatch repair–deficient (dMMR) and microsatellite instability–high (MSI-H) tumors. These findings prompted the US Food and Drug Administration to approve dostarlimab plus chemotherapy as the first new frontline treatment option for dMMR/MSI-H primary advanced or recurrent endometrial cancer.

For the RUBY phase 3 trial 494 patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned to receive either dostarlimab (500 mg) or placebo, plus carboplatin and paclitaxel every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. Dostarlimab, an anti-PD-1, was used because he combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer. In the dMMR–MSI-H population, estimated progression-free survival at 24 months was 61.4% in the dostarlimab group and 15.7% in the placebo group; in the overall population, progression-free survival at 24 months was 36.1% and 18.1% respectively. Overall survival at 24 months was 71.3%with dostarlimab and 56.0% with placebo. Common adverse events were nausea, alopecia and fatigue, with severe and serious adverse events more frequent in the dostarlimab group than in the placebo group. «Substantial unprecedented and clinically meaningful long-term benefit was observed in dMMR/MSI-H subgroup along with a safety profile of the combination manageable and generally consistent with that of the individual drugs», lead study author Mansoor Raza Mirza said during the simultaneous presentation of data at The Society of Gynecologic Oncology 2023 Meeting on Women’s Cancer. «Therefore, dostarlimab plus carboplatin/paclitaxel can represent a new standard of care for patients with primary advanced and recurrent endometrial cancer».