The Rationale for Dostarlimab Monotherapy In MSI-H and MSS Endometrial Cancer

Ana Oaknin, MD, head of the Gynecologic Tumors Unit, Vall d’Hebron University Hospital, and principal investigator, Gynecological Malignancies Group, explains the rationale for analyzing anti—PD-1 monotherapy with dostarlimab(TSR-042) in patients with microsatellite instability–high (MSI-H) and microsatellite stable (MSS) endometrial cancer. 

With limited options available for treating women with advanced or recurrent endometrial cancer, the phase I/II GARNET studyanalyzed 125 patients—33% with MSI-H endometrial cancer, 63% with MSS disease, and the remaining with unknown MSI status—receiving treatment with dostarlimab 500 mg in 4 doses every 3 weeks. Patients then received 1000 mg of the anti—PD-1 monotherapy every 6 weeks until disease progression. The study found clinically relevant overall response rates (ORRs). The full population showed a 30% ORR, MSI-H patients had a 49% ORR, and MSS patients had a 20% ORR.

The purpose for this study was to look at anti—PD-1 monotherapy across multiple patient populations for endometrial cancer, says Oaknin. It addresses the limitations with standard therapies and the need for a therapy that targets MSS, unlike the commonly used treatment, pembrolizumab (Keytruda), which was approved specifically for the treatment of patients with MSI-H endometrial cancer.