Mismatch repair-deficient and microsatellite instability-high endometrial cancers are highly immunogenic tumors that derive substantial benefit from immune checkpoint inhibition. Previous analyses from the Phase III RUBY trial established dostarlimab plus carboplatin-paclitaxel as a highly effective frontline treatment, demonstrating significant progression-free survival and overall survival benefits compared with chemotherapy alone.

A notable feature of the RUBY trial was the plateau observed in the progression-free survival curve, raising the possibility that a subset of patients may achieve long-term remission and potentially curative outcomes. To further investigate this hypothesis, researchers conducted an updated long-term analysis using mixture cure modeling (MCM), a statistical approach designed to estimate the proportion of patients who may remain permanently free from disease recurrence. At a median follow-up of 55.6 months, the analysis provides the most mature assessment to date of long-term outcomes in this patient population.

Efficacy Outcomes:

• 4-year PFS rate: 57.9% with dostarlimab + carboplatin/paclitaxel versus 15.7% with chemotherapy alone.
• Only four new progression events were reported during an additional 2.5 years of follow-up, highlighting durable disease control.
• Mixture cure modeling estimated that 54% of patients (95% CI: 35–72%) treated with dostarlimab plus chemotherapy may achieve long-term curative outcomes.

KOL Insights

“The sustained plateau in progression-free survival suggests the presence of a potential cure fraction, where a subset of patients experiences a very low long-term risk of disease progression. Cure modeling further supports the existence of distinct patient groups, with some achieving durable disease control while others continue to face a risk of progression over time.”– Expert Opinion

“RUBY demonstrated durable remissions and long-term survival benefits in patients with dMMR endometrial cancer, suggesting the potential for curative outcomes in a subset of patients and marking a significant advance in the treatment landscape.”– Expert Opinion

Conclusion

Endometrial cancer is the most common gynecologic malignancy in developed countries, with incidence continuing to rise globally. Approximately 25–30% of advanced or recurrent endometrial cancers are characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status, a molecular subtype associated with high tumor immunogenicity and increased responsiveness to immune checkpoint inhibitors.

The updated long-term RUBY analysis showed durable disease control with dostarlimab plus carboplatin-paclitaxel in patients with dMMR/MSI-H advanced or recurrent endometrial cancer, with 57.9% remaining progression-free at four years. Importantly, mixture cure modeling estimated that approximately 54% of patients may achieve long-term curative outcomes, suggesting that frontline dostarlimab-based therapy has the potential to significantly improve long-term prognosis and redefine treatment expectations in this patient population.