Four-year follow-up from the phase III RUBY clinical trial showed durable long-term benefit with front-line dostarlimab-gxly, a PD-1 blocker, plus carboplatin/paclitaxel in patients with mismatch repair–deficient/microsatellite instability–high (dMMR/MSI-H) primary advanced or recurrent endometrial cancer, raising the possibility of curative intent in at least a subset of patients.¹ Matthew A. Powell, MD, who presented the update at the 2026 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer, described the most important long-term takeaway as “profound and sustained disease control.” In this subgroup, the 4-year overall survival rate was 72.8% with dostarlimab plus chemotherapy vs 40.3% with placebo plus chemotherapy, and median overall survival remained unreached after a median follow-up of 55.6 months.

Matthew A. Powell, MD

For more than a decade, carboplatin/paclitaxel alone had been standard first-line treatment for primary advanced or recurrent endometrial cancer, but long-term outcomes were poor. In an interview conducted with The ASCO Post after the presentation, Dr. Powell said the 5-year survival rate for such patients had been 18.4% before immunotherapy entered practice.

Dr. Powell, of Washington University School of Medicine and Siteman Cancer Center, said the RUBY update shows the field is moving beyond short-term disease control. In his interview, he said survival in this subgroup now appears to “approach that of a matched population without cancer,” while also cautioning that “declaring cure is always difficult.”

RUBY previously showed significant improvements in progression-free and overall survival with dostarlimab plus chemotherapy in the overall population, with especially strong benefit in the dMMR/MSI-H subgroup. This analysis, which is the longest follow-up of any immunotherapy phase III study in this setting, focused on long-term outcomes, conditional survival, and safety in that subgroup.

Study Design

The trial randomly assigned patients with stage III or IV disease or first recurrent endometrial cancer to dostarlimab plus carboplatin/paclitaxel followed by dostarlimab maintenance for up to 3 years, or to placebo plus chemotherapy followed by placebo. It enrolled 53 patients with dMMR/MSI-H disease in the dostarlimab arm and 65 in the placebo arm for this subgroup analysis. Baseline characteristics were generally similar between the groups.

Median age was 61 years in the dostarlimab arm and 66 years in the placebo arm. About half the patients in each group had recurrent disease, most had endometrioid histology, and ECOG performance status distributions were similar.

Durable Progression-Free Survival

At 55.6 months of median follow-up, progression-free survival was not reached in the dostarlimab arm vs 7.7 months in the placebo arm (hazard ratio [HR] = 0.30). Four-year progression-free survival rates were 57.9% and 15.7%, respectively.

Dr. Powell highlighted what he viewed as one of the most striking findings: only four new progression events occurred with an additional 2.5 years of follow-up, and the plateau seen on the progression-free survival curve had been maintained. In his interview, he said the 4-year data show “profound and durable disease control” and that the sustained flattening of the curve raises the possibility of long-term benefit for at least a subset of patients.

Overall Survival Remained Unreached

The overall survival data were similarly notable, according to Dr. Powell. Median overall survival was not reached with dostarlimab plus chemotherapy vs 32.8 months with placebo plus chemotherapy (HR = 0.34), corresponding to a 66% reduction in the risk of death. Four-year overall survival rates were 72.8% and 40.3%, respectively.

Dr. Powell called the continued absence of a median overall survival in the dostarlimab arm “a compelling finding” after more than 4.5 years of follow-up.

“This signifies an unprecedented extension in survival when adding dostarlimab to chemotherapy compared to chemotherapy alone,” he told The ASCO Post. “We’re moving beyond managing disease progression to actively aiming for sustained, long-term survival, again, challenging historical prognosis for these patients.”

Notably, about 71% of patients in the placebo arm who received follow-up anticancer treatment went on to receive immunotherapy, yet the overall survival curves did not converge. Dr. Powell said this suggests that the timing of immunotherapy may be important, possibly reflecting “some important interaction with chemotherapy or timing with the immunotherapy agent,” and warrants further investigation.

Conditional Survival as a Counseling Tool

A post hoc conditional survival analysis was included to help clinicians counsel patients who remain progression-free or alive at landmark time points. In the dostarlimab arm, patients who were progression-free at 2 years had a 91.7% probability of remaining progression-free and alive at 4 years. Patients alive at 1 and 2 years had 84.0% and 88.0% probabilities, respectively, of remaining alive at 4 years.

Dr. Powell said this type of analysis can help turn a difficult and often vague conversation into a more data-driven one. He called conditional survival “a more personalized tool” for discussing the likelihood of long-term benefit, noting that patients and their families often ask whether the potential for surviving to 1 or 2 years changes the outlook. He said the estimates improved with each year a patient remained alive and that the analysis was designed to help answer exactly that question.

“How and when an oncologist approaches a discussion of long-term survival with their patients will vary, but in my opinion, it should be based on data, noting both what we know from it and the potential limitations, and balance a realistic and hopeful view,” he explained. “These data from RUBY Part 1 lay the groundwork for initiating these types of discussions with patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer.”

The analysis also feeds into the increasingly prominent question of cure. Dr. Powell stopped short of declaring cure, but said the durability of the curves, the unreached median overall survival, and the observation that survival may approach that of a matched noncancer population all support considering the possibility of sustained long-term benefit, adding that longer follow-up is continuing.

Safety

No new safety signals emerged with longer follow-up, and dostarlimab-related immune-related adverse events remained low over time. The most common immune-related adverse events in the dostarlimab arm were hypothyroidism, arthralgia, maculopapular rash, increased ALT, rash, and hyperthyroidism, with grade 3 or higher events remaining uncommon.

A New Benchmark in dMMR/MSI-H Disease

According to the RUBY investigators, these 4-year data suggest the potential for curative intent in this population.

In his interview, Dr. Powell described the biggest remaining question as whether similarly profound long-term outcomes can be achieved in the broader patient population, and how best to identify the patients most likely to benefit. For now, the RUBY update strengthens the case that front-line dostarlimab plus chemotherapy has fundamentally changed what’s possible for patients with dMMR/MSI-H advanced or recurrent endometrial cancer. 

DISCLOSURE: This study (NCT03981796) was funded by GSK. Dr. Powell reports consulting fees from AstraZeneca, Clovis Oncology, Eisai, GSK/Tesaro, MSD, and Seagen/Pfizer.

REFERENCE

1. Powell MA, Zub O, Gilbert L, et al: Four-year survival outcomes with dostarlimab plus chemotherapy in dMMR/MSI-H primary advanced or recurrent endometrial cancer in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. 2026 SGO Annual Meeting. Abstract 143. Presented on April 12, 2026.

EXPERT POINT OF VIEW 

Four-year follow-up from the phase III RUBY clinical trial showed durable long-term benefit with front-line dostarlimab plus carboplatin/paclitaxel in patients with mismatch repair–deficient/microsatellite instability–high (dMMR/MSI-H) primary advanced or recurrent endometrial cancer. Matthew A. Powell, MD, presented the update at the 2026 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.¹ In her discussion of the session, Vicky Makker, MD, of Memorial Sloan Kettering Cancer Center, called the 4-year RUBY data “truly transformative” and said the trial now sets the front-line benchmark for dMMR/MSI-H advanced or recurrent endometrial cancer. She argued that RUBY stands out among front-line immunotherapy studies because of its maturity, visible 4-year plateau, and durable overall survival signal.

Vicky Makker, MD

She also highlighted the heavy crossover context, noting that the survival curves remained separated despite subsequent immunotherapy use in many patients assigned to placebo. In her view, that factor makes RUBY some of the strongest evidence yet that front-line benefit may not be fully recaptured later. “Early intervention is superior to late rescue,” she said.

Dr. Makker used the RUBY results to raise the next set of questions for the field: whether deep responders need the full 3 years of maintenance; whether chemotherapy can eventually be reduced or omitted in selected patients; how resistance develops in dMMR disease; and how best to treat recurrence after front-line chemoimmunotherapy. 

DISCLOSURE: Dr. Makker reported institutional grants or contracts with AstraZeneca, Bristol Myers Squibb, Cullinan Oncology, DualityBio, Eisai, Faeth Therapeutics, Jazz, Karyopharm Therapeutics, Merck, Takeda, and Zymeworks; has received travel expenses from AstraZeneca, Karyopharm, and Merck; and has served as a consultant for Antares Therapeutics, Clovis Oncology, Cullinan Oncology, DualityBio, Eisai, Faeth Therapeutics, GenMab, GlaxoSmithKline, Immunocore, Incyte, iTeos Therapeutics, Karyopharm Therapeutics, Jazz Pharmaceuticals, Lilly, Merck, Mereo BioPharma, MorphoSys, MSD, Novartis, Ottimo Pharma, Regeneron, Scorpion Therapeutics, Stemline Therapeutics, Sutro Biopharma, and Zymeworks.

REFERENCE

1. Powell MA, Zub O, Gilbert L, et al: Four-year survival outcomes with dostarlimab plus chemotherapy in dMMR/MSI-H primary advanced or recurrent endometrial cancer in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. 2026 SGO Annual Meeting. Abstract 143. Presented on April 12, 2026.