Dostarlimab/Chemo Shows Curative Potential in dMMR/MSI-H Advanced Endometrial Cancer

A post hoc analysis of the phase 3 RUBY trial (NCT03981796), presented at the 2026 American Society of Clinical Oncology Annual Meeting and simultaneously published in Gynecologic Oncology, indicates that a significant proportion of patients with mismatch repair–deficient/microsatellite instability–high (dMMR/MSI-H) primary advanced or recurrent endometrial cancer treated with dostarlimab (Jemperli) plus carboplatin-paclitaxel (CP) may have curative potential.^1,2

With up to 4.5 years of follow-up, mixture cure model data revealed that approximately 54% (95% CI, 35%-72%) of patients receiving dostarlimab plus CP in the frontline setting were estimated to be “cured” (defined as free of recurrence- and disease-related mortality risks) vs 14% with placebo plus CP. The 4-year progression-free survival (PFS) rate was 57.9% (95% CI, 42.3%-70.6%) with the dostarlimab combination vs 15.7% (95% CI, 7.2%-27.0%) with CP alone.

Only 4 new progression events were reported over an additional 2.5 years of follow-up since the initial PFS analysis in this subpopulation, underscoring the durability of disease control in this group.

Additionally, at 4 years, the median OS had not been reached in patients receiving the dostarlimab regimen compared with 32.8 months (95% CI, 21.6-not estimable) in the control arm, suggesting that the durable disease control seen with dostarlimab may translate into sustained survival gains for a substantial subset of patients.

“RUBY demonstrated a sustained remission and long-term survival outcomes in patients with [dMMR] endometrial cancer with a potential for curative intent, which makes this exciting for all of us,” presenting author Matthew A. Powell, MD, of Washington University School of Medicine Siteman Cancer Center, said during the presentation of data.

RUBY: Background and Rationale

The RUBY trial is a randomized, double-blind, phase 3 study evaluating dostarlimab plus CP vs placebo plus CP in patients with primary advanced or recurrent endometrial cancer.³ In part 1 of the trial, dostarlimab plus CP demonstrated statistically significant PFS improvement and clinically meaningful overall survival (OS) benefit in the dMMR/MSI-H population.⁴ Median PFS was not reached in the dostarlimab/CP arm compared with 7.7 months for CP alone in this subgroup.

A subsequent plateau in the PFS Kaplan-Meier curve beginning at 12 months suggested that this subset of patients had achieved durable disease control. This observation prompted investigators to apply mixture cure modeling to the trial’s long-term PFS data to quantify the proportion of patients with curative potential and to characterize PFS among those who remained uncured.

“From an oncologic perspective, sustained plateau in PFS is consistent with the presence of a cure fraction, meaning a subset of patients in whom progression becomes very low likelihood over time,” Powell said during the presentation. “Mixed tier models allow us to assess whether there is heterogeneity within this population estimate, and if the subgroup of patients whose risk of progression becomes very low over the long term, compared [with] others who maintain a risk of progression.”

Long-Term Safety Findings

With an additional 2.5 years of follow-up, no new safety signals were identified in the dMMR population treated with the dostarlimab combination. The safety profile remained consistent with prior analyses of the RUBY trial, supporting the long-term tolerability of the regimen.

Immune-related adverse events (IRAEs) continued to occur at low rates throughout the study, and the overall incidence remained low despite extended follow-up. The most common dostarlimab-related IRAEs noted included hypothyroidism, arthralgia, maculopapular rash, alanine aminotransferase increase, rash, and hyperthyroidism.

Clinical Implications and Utility

The updated RUBY analysis corroborates growing evidence that frontline immunotherapy combined with chemotherapy may achieve durable disease control—and potentially curative outcomes—in a subset of patients with dMMR/MSI-H advanced or recurrent endometrial cancer. The cure fraction estimated by the model in patients receiving the dostarlimab regimen represents nearly a 4-fold increase in the proportion of patients predicted to achieve long-term remission.

Beyond demonstrating sustained PFS and OS benefits, the findings may offer clinicians a framework for discussing long-term prognosis with patients. Conditional survival analyses showed that patients who remained progression-free at 2 years had greater than a 90% probability of remaining progression-free at 4 years, whereas those alive at 1, 2, or 3 years had more than an 80% likelihood of being alive at 4 years.

Although the cure model findings remain exploratory and require additional follow-up for validation, Powell suggested that these data support the use of up-front immunotherapy in dMMR endometrial cancer and may help inform conversations regarding the potential for long-term remission and survival.

“This analysis may assist all of us in communicating long-term survival outcomes in our patients receiving this regimen,” Powell said.

DISCLOSURES: Powell reported a consulting or advisory role with AstraZeneca, Clovis Oncology, Eisai, MSD, Seagen/Pfizer, and Tesaro/GSK.

REFERENCES

1. Powell, MA. Long-term survival rates and cure modeling with dostarlimab plus chemotherapy in mismatch repair deficient/microsatellite instability high (dMMR/MSI-H) primary advanced or recurrent endometrial cancer in the ENGOT-EN6-NSGO/ GOG-3031/RUBY trial. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 5501.

2. Powell MA, Roed H, Willmott LJ, et al. Four-year survival outcomes with dostarlimab plus chemotherapy in mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer in the RUBY trial. Gynecol Oncol. Published online May 29, 2026. doi:10.1016/j.ygyno.2026.05.008

3. A study to evaluate dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in participants with recurrent or primary advanced endometrial cancer (RUBY). ClinicalTrials.gov. Updated September 3, 2025. Accessed May 29, 2026. https://clinicaltrials.gov/study/NCT03981796

4. Powell MA, Bjørge L, Willmott L, et al. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin–paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial. Ann Oncol. 2024;35(8):728-738. doi:10.1016/j.annonc.2024.05.546