Adding immunotherapy to standard chemotherapy for the first-line treatment of advanced or the first recurrence of endometrial cancer significantly improved progression-free survival compared to chemotherapy alone, according to data presented by Mansoor Raza Mirza, MD, and colleagues at the March European Society for Medical Oncology Virtual Plenary (Abstract VP2-2023). Findings from the phase III RUBY trial (ENGOT-EN6-NSGO/GOG3031)—also presented concurrently in a late-breaking session of the Society of Gynecologic Oncology 2023 Annual Meeting on Women’s Cancer and published in The New England Journal of Medicine—showed a doubling of progression-free survival at 24 months with the combination of the PD-1 inhibitor dostarlimab-gxly plus carboplatin and paclitaxel vs chemotherapy alone (36.1% vs 18.1%, P < .001). The effect was even more pronounced in patients with mismatch repair–deficient, microsatellite instability–high tumors (61.4% vs 15.7%, P < .001).
“This is the biggest news for patients with endometrial cancer in more than 30 years,” said Dr. Mirza, Chief Oncologist at Rigshospitalet, Copenhagen University Hospital, and Medical Director of the Nordic Society of Gynecologic Oncology–Clinical Trial Unit, Denmark. Dr. Mirza is also the principal investigator of the RUBY trial. “These results have shown an unprecedented improvement in progression-free survival as a result of adding immunotherapy to standard chemotherapy, especially in the 25% of patients with so-called ‘hot’ endometrial tumors that have deficient DNA mismatch repair mechanisms.”
This is the biggest news for patients with endometrial cancer in more than 30 years... These results have shown an unprecedented improvement in progression-free survival as a result of adding immunotherapy to standard chemotherapy, especially in the 25% of patients with so-called ‘hot’ endometrial tumors that have deficient DNA mismatch repair mechanisms.— Mansoor Raza Mirza, MD
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Background and Rationale
As Dr. Mirza reported, endometrial cancer is the sixth most common cancer in women worldwide, with over 400,000 new cases per year. Localized disease is curable with surgery, he said, but in advanced cases, the 5-year survival rate falls to 20%. Recent advancements in the understanding of endometrial cancer have led to the identification of four molecular subgroups of the disease, which has prompted European and U.S. guidelines to recommend testing for tumor DNA repair status for risk classification and potentially to help guide treatment and improve outcomes.
Despite these advancements, chemotherapy with carboplatin and paclitaxel remains the standard treatment for advanced disease. Although effective in nearly 50% of patients, most experience disease progression within a year, Dr. Mirza noted.
RUBY Trial: Methods and Results
The RUBY trial is a phase III, global, randomized, double-blind, multicenter, placebo-controlled study evaluating the efficacy and safety of dostarlimab combined with standard chemotherapy (carboplatin and paclitaxel) in patients with advanced or recurrent endometrial cancer. The primary endpoints were progression-free survival by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival.
The recently published and presented results showed that the median progression-free survival was 11.8 months in patients treated with dostarlimab and standard chemotherapy, compared to 7.9 months in those treated with standard chemotherapy and placebo. In the overall population, progression-free survival at 24 months was 36.1% in the dostarlimab group and 18.1% in the placebo group; overall survival at 24 months was 71.3% with dostarlimab and 56.0% with placebo.
In patients with ‘hot’ tumors with deficient mismatch repair or high microsatellite instability, median progression-free survival could not be estimated in the immunotherapy plus chemotherapy group due to too few cancers progressing during the 25-month follow-up. However, median progression-free survival was only 7.7 months in the chemotherapy-plus-placebo group.
“In the patients with ‘hot’ tumors who had the additional immunotherapy, the 72% benefit in progression-free survival was much larger than the 50% we expected to see, and in those with ‘cold’ tumors, we saw a moderate effect of immunotherapy on progression-free survival,” said Dr. Mirza.
The safety profile of dostarlimab combined with chemotherapy was generally consistent with the safety profile of each drug. Discontinuation of dostarlimab or placebo due to treatment-emergent adverse events occurred in 17.4% of patients receiving dostarlimab plus chemotherapy and 9.3% of patients receiving placebo plus chemotherapy.
Disclosure: Dr. Mirza reported financial relationships with AstraZeneca, Biocad, GSK, Merck, Roche, Zailab, Karyopharm, Ultimovacs, Apexigen, and Deciphera. For full disclosures of the study authors, visit oncologypro.esmo.org or nejm.org.
