Real-World Data Verify Safety, Efficacy of Dostarlimab/Chemo in Endometrial Cancer

Patients with dMMR tumors saw better PFS relative to those with pMMR disease, and patients with stage III disease also saw improvemed PFS relative to those with stage IV or recurrent disease.

Real-world treatment with dostarlimab-gxly (Jemperli) plus carboplatin and paclitaxel in patients with advanced or recurrent endometrial cancer produced comparable progression-free survival (PFS) outcomes to treatment in the phase 3 RUBY trial (NCT03981796), according to data from a retrospective analysis presented by Taliya Lantsman, MD, and colleagues at the 2025 SGO Annual Meeting on Women’s Cancer.¹

Findings from this analysis showed that patients with mismatch repair–deficient (dMMR) tumors demonstrated improved PFS relative to those with mismatch repair–proficient (pMMR) disease, and those with stage III cancer demonstrated improved PFS compared with patients with stage IV or recurrent disease.

“[In this real-world analysis], PFS with dostarlimab plus carboplatin and paclitaxel is comparable to efficacy outcomes shown in the RUBY trial,” Lantsman, a second-year hematology/oncology fellow at Beth Israel Deaconess Medical Center in Boston, Massachusetts, explained in her presentation.¹

Findings from part 1 of the RUBY trial, which supported the FDA approval of dostarlimab with carboplatin and paclitaxel on August, 1, 2024, for patients with primary advanced or recurrent endometrial cancer, demonstrated a 24-month PFS rate of 36.1% (95% CI, 29.3%-42.9%) with dostarlimab vs 18.1% (95% CI, 13.0%-23.9%) with placebo (HR, 0.64; 95% CI, 0.51-0.80; P < .001).^2,3

Patients with dMMR/microsatellite instability–high disease also achieved substantial benefit with the dostarlimab regimen, with an estimated 24-month PFS rate of 61.4% (95% CI, 46.3%-73.4%) vs 15.7% (95% CI, 7.2%-27.0%) with placebo.³

Study Design and Patient Demographics

A total of 27 patients with stage III, IV, or recurrent endometrial cancer were included in the real-world retrospective analysis evaluating the safety and efficacy of dostarlimab in combination with carboplatin and paclitaxel.¹

Patients were required to have received the combination treatment between July 1, 2023, and August 14, 2024. The study was designed to assess outcomes in a real-world setting following the incorporation of dostarlimab into first-line chemotherapy regimens, as supported by findings from the GARNET (NCT02715284) and RUBY trials.

The median age at enrollment was 63 years and the cohort included Caucasian (59%), African American (26%), and Asian (15%) patients. Notably, 30% of patients had dMMR tumors.

At the time of dostarlimab treatment initiation, 56% of patients had stage IV disease, 22% had recurrent disease, and 22% had stage III disease (IIIA, 4%; IIIC1, 11%; IIIC2, 7%). Most patients had endometrioid (37%) or serous (26%) histology, while 11% had carcinosarcoma, and 27% were classified under other histologic subtypes.

Most patients (74%) had an ECOG performance status (PS) of 0, with 15% having an ECOG PS of 1 and 11% having an ECOG PS of 2. Additionally, most patients (70%) underwent prior surgery.

The median treatment duration was 168 days (IQR, 106-254), and the median follow-up time was 188 days (IQR, 153-253). Reasons for dostarlimab discontinuation included disease progression (70%) and immune adverse effects (9%).

Among patients with stage III disease, all received radiation therapy, and none experienced immune-related toxicities. Of the 17 patients who did not progress, 71% had low-risk endometrioid histology. Of the 27 patients included in the analysis, a total of 7 patients (28%) experienced disease progression.

“In patients who received radiation, none experienced immune-related toxicities, and the safety profile was consistent with that of the individual components of the treatments. For the patients who progressed, most had high-grade histologies and progressed around the time of chemotherapy completion,” Lantsman concluded.

References

1. Lantsman T, Jia L, Edmiston C, Shea M, Widick P. Real-world RUBY: safety and efficacy of combination chemotherapy plus dostarlimab in advanced endometrial cancer. Presented at: 2025 SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Abstract 1280.
2. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA. August 1, 2024. Accessed March 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy
3. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158. doi:10.1056/NEJMoa2216334