Dostarlimab and Chemotherapy Improve Treatment Outcomes in Older Endometrial Cancer Patients

In a significant advancement for gynecological oncology, a combination of dostarlimab (brand name Jemperli) and chemotherapy has been shown to markedly extend the time to first and second subsequent therapies in patients with primary advanced or recurrent endometrial cancer, irrespective of age. This was revealed in a post hoc analysis of the phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial, with findings presented at the 2025 European Society for Medical Oncology (ESMO) Gynecological Cancers Congress.

The study, which enrolled 494 patients, found that the median time to first subsequent therapy (TFST) increased significantly from 10.2 months (95% CI, 9.1-10.9) in those receiving a placebo regimen to 15.3 months (95% CI, 12.3-20.1) in the dostarlimab cohort. Similarly, the median time to second subsequent therapy (TSST) improved from 19.9 months (95% CI, 16.3-23.1) to 31.3 months (95% CI, 24.6-40.8) for the same groups, demonstrating a hazard ratio (HR) of 0.67 (95% CI, 0.53-0.85) for TSST.

Among patients aged 70 years or older, the dostarlimab regimen led to an 8.7-month extension in TFST and an 8.0-month increase in TSST compared to the placebo. These results are particularly noteworthy given the demographic's historical underrepresentation in clinical trials, highlighting the importance of including older patients in therapeutic research.

Dr. Ilana Cass, MD, a lead investigator and Professor of Obstetrics and Gynecology at Geisel School of Medicine, Dartmouth University, emphasized the relevance of these findings: "With more than three years of follow-up, these results demonstrate the efficacy and tolerability of frontline dostarlimab plus carboplatin and paclitaxel in patients aged 70 years or older, reinforcing its potential as the standard of care."

The trial, which followed rigorous protocols, randomized participants to receive either dostarlimab plus carboplatin and paclitaxel or placebo combined with the same chemotherapy regimen. Patients were followed for efficacy outcomes including progression-free survival (PFS) and overall survival (OS), alongside safety assessments across different age groups.

The results not only indicate substantial efficacy but also reveal acceptable safety profiles across age demographics. Although the incidence of immune-related adverse effects (irAEs) was higher in patients aged 70 years and older, the overall death rate due to treatment-emergent adverse events (TEAEs) was lower in this group (1.4%) compared to younger patients (2.4%).

This study builds upon previous findings that supported the July 2023 FDA approval of dostarlimab in combination with carboplatin and paclitaxel for adult patients with primary advanced or recurrent endometrial cancer characterized by mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). The consensus among leading oncologists is that dostarlimab's efficacy and safety profile warrant its use as a frontline treatment in all patients with this type of cancer, regardless of age.

The implications of these findings extend beyond immediate clinical practices, potentially shaping future guidelines and treatment protocols. As Dr. Cass and her co-authors concluded, the combination of dostarlimab and chemotherapy represents a promising standard of care that could enhance survival outcomes for a vulnerable patient population. In light of these developments, the oncology community is urged to reassess treatment strategies for older patients, ensuring they receive the most effective therapies available.