Dr Mirza on the FDA Approval of Dostarlimab Plus Chemotherapy in dMMR/MSI-H Endometrial Cancer

Mansoor Raza Mirza, MD, chief oncologist, Department of Oncology, Rigshospitalet, Copenhagen University Hospital, discusses the significance of the FDA approval of dostarlimab-gxly (Jemperli) in combination with chemotherapy in patients with mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) endometrial cancer.

On July 31, 2023, the FDA approved dostarlimab plus carboplatin and paclitaxel followed by dostarlimab monotherapy for adult patients with dMMR or MSI-H primary advanced or recurrent endometrial cancer. The regulatory decision was supported by interim findings from part 1 of the phase 3 RUBY trial (NCT03981796), in which the combination led to a 71% reduction in the risk of disease progression or death vs chemotherapy alone.

Prior to this approval, the standard of care for patients with stage III/IV or relapsed dMMR/MSI-H endometrial cancer was carboplatin plus paclitaxel, Mirza says. Previously, the phase 3 GOG0209 trial (NCT00063999), which investigated first-line carboplatin plus paclitaxel vs paclitaxel plus doxorubicin and cisplatin (TAP) in patients with advanced endometrial cancer, showed that carboplatin plus paclitaxel was noninferior to TAP. However, the median overall survival (OS) with carboplatin plus paclitaxel was 37 months compared with 41 months with TAP (HR, 1.002; 90% CI, 0.9-1.12), demonstrating an unmet need in this patient population, Mirza explains.

Approximately 30% of patients with endometrial cancer have dMMR disease, and the RUBY trial aimed to determine whether a combination of immunotherapy and chemotherapy could enhance the efficacy of each of these agents in this population. The coprimary end points of RUBY were progression-free survival (PFS) in the dMMR population, PFS in the overall population, and OS. A total of 494 patients were randomly assigned 1:1 to receive either carboplatin plus paclitaxel plus dostarlimab or placebo for 6 cycles, followed by dostarlimab or placebo monotherapy every 6 weeks for a maximum of 3 years.

Notably, RUBY allowed patients who had received neoadjuvant or adjuvant systemic therapy and relapsed at least 6 months after treatment completion, as well as those with rare endometrial tumors, such as carcinosarcoma, Mirza concludes.