Adding the PD-1 inhibitor dostarlimab to standard chemotherapy provides sustained survival benefits for patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) advanced endometrial cancer, according to updated results from the phase 3 RUBY trial.

At 4 years, overall survival was just under 73% vs 40% among patients who received dostarlimab plus carboplatin-paclitaxel vs chemotherapy alone for a 66% reduction in the risk for death.

The durable survival benefit suggests “the potential for curative intent,” said investigator Vladyslav S. Sukhin, MD, of the Grigoriev Institute for Medical Radiology and Oncology at the National Academy of Medical Sciences of Ukraine in Kharkiv, Ukraine.

He presented the findings at the ESMO Gynecological (ESMO Gyn) Cancers Congress 2026, held in Copenhagen. The full study was published in Gynecologic Oncology.

About 25%-30% of patients with endometrial cancer have dMMR/MSI-H disease. While chemotherapy has long been the standard treatment for advanced or recurrent endometrial cancer, dMMR/MSI-H tumors have a high mutational burden that makes them particularly sensitive to immune checkpoint blockade.

Earlier data from the RUBY trial showed that adding dostarlimab to carboplatin-paclitaxel improved 2-year overall survival among patients with stage III-IV or recurrent endometrial cancer — particularly those with dMMR/MSI-H tumors.

The updated data come from 118 trial patients who had dMMR/MSI-H disease; 53 were randomized to receive dostarlimab plus chemotherapy, while 65 received placebo plus chemotherapy. Chemotherapy was given every 3 weeks for six cycles, followed by dostarlimab or placebo monotherapy every 6 weeks for up to 3 years or until disease progression.

At 4 years, Sukhin reported, progression-free survival was 58% vs just under 16% among patients receiving dostarlimab vs chemotherapy alone, representing a 70% reduction in the risk for disease progression or death.

Median overall survival was 32.8 months in the chemotherapy-only arm, while it was not yet reached in the dostarlimab arm.

Sukhin emphasized that in the 2.5 years since the prior progression-free survival analysis, only four new progression events were recorded among patients treated with dostarlimab.

Study discussant Nicole Concin, MD, PhD, of the University Hospital Vienna, Austria, called the data “really impressive.”

She noted that the progression-free survival curve in the immunotherapy arm had effectively plateaued, indicating “durable disease control and the potential for cure.”

Like Sukhin, Concin underscored the low number of new progression events since the prior analysis: Patients who are progression-free at 2 years, she said, have a more than 90% chance of remaining so at 4 years.

“These data are not only confirming our decision to add immunotherapy in this patient population, but they also help us with counseling our patients that sit in front of us,” Concin said.

Sukhin also reported findings on best overall response and long-term disease control with immunotherapy — the upshot being that durable benefits were not limited to patients with complete response.

Overall, he said, about one third of patients in the dostarlimab arm (17 of 53) achieved a complete response. Of these, three experienced subsequent progression or death, and among the 12 patients with a confirmed complete response at the 1-year landmark, only one had documented progression at 4 years.

However, Sukhin said, patients with partial responses or stable disease also showed long-term progression-free survival benefits.

As reported in the published paper, there were no new safety signals over the longer term. Grade 3 or higher treatment-related adverse events occurred in 61.5% vs 49% of patients in the dostarlimab arm vs chemotherapy-only arm. The most common in either arm included alopecia, fatigue, nausea, peripheral neuropathy, arthralgia, and diarrhea.

Three quarters of patients receiving dostarlimab had an immune-related adverse event; over half were considered to be related to the drug — most often hypothyroidism, arthralgia, and maculopapular rash. Five patients had a grade 3 or worse rash or maculopapular rash.

Just over 19% vs 12% of patients in the dostarlimab arm vs the placebo arm discontinued treatment due to adverse events. There were two deaths due to treatment-related adverse events in the dostarlimab arm and none in the placebo arm.

The RUBY trial was funded by GSK. Sukhin reported having financial relationships with GSK and AstraZeneca. Concin reported having financial relationships with numerous sources, including Amgen, GSK, Medtronic, Roche, and Medscape Oncology.