European Commission Approves Dostarlimab Plus Chemo for All Advanced/Recurrent Endometrial Cancer

The European Commission (EC) has approved frontline dostarlimab (Jemperli) plus carboplatin and paclitaxel for the treatment of all adult patients with primary advanced or recurrent endometrial cancer who are candidates for systemic therapy.1 This approval expands the previous European Union (EU) indication for dostarlimab plus chemotherapy to include patients with mismatch repair–proficient (pMMR)/microsatellite stable (MSS) tumors, which comprise approximately 75% of patients diagnosed with endometrial cancer.

The EC’s decision to expand the indication of the combination was supported by findings from part 1 of the 2-part, global, randomized, multicenter, double-blind phase 3 RUBY trial (NCT03981796), which compared dostarlimab plus carboplatin and paclitaxel followed by dostarlimab monotherapy vs carboplatin plus paclitaxel plus placebo followed by placebo alone in patients with primary advanced or recurrent endometrial cancer. Findings from RUBY part 1, which were presented at the 2024 SGO Annual Meeting and subsequently published in Annals of Oncology, showed that at the 2.5-year landmark analysis, the overall survival (OS) rate with dostarlimab plus chemotherapy (n = 245) was 61% (95% CI, 54%-67%) vs 49% (95% CI, 43%-55%) with chemotherapy alone (n = 249). The dostarlimab regimen led to a 31% reduction in the risk of death vs chemotherapy plus placebo (HR, 0.69; 95% CI, 0.54-0.89; nominal P = .002).1,2

“Clinicians have been waiting for years for an immuno-oncology–based option that can meaningfully improve OS outcomes for patients with pMMR/MSS primary advanced or recurrent endometrial cancer,” Mansoor Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark and the principal investigator of the RUBY trial, stated in a news release.1 “The expanded approval represents a significant advance that delivers on this hope, now for patients with both MMR-deficient/microsatellite instability–high and pMMR/MSS tumors.”

At the second interim analysis of RUBY at an expected median follow-up of 37.2 months (range, 31.0-49.5), treatment with dostarlimab plus chemotherapy led to a median OS of 44.6 months (95% CI, 32.6-not reached) vs 28.2 months (95% CI, 22.1-35.6) with chemotherapy alone.2

“For the first time, all patients with primary advanced or recurrent endometrial cancer in the EU have an approved immuno-oncology–based treatment that has shown a statistically significant and clinically meaningful OS benefit,” Hesham Abdullah, senior vice president and global head of Oncology R&D at GSK, added in the news release.1 “We’re proud [dostarlimab] continues to redefine the treatment landscape for patients.”

Additional efficacy findings from RUBY part 1 showed that in the pMMR/MSS population, at 55% OS maturity, the dostarlimab regimen was associated with a 21% reduction in the risk of death (HR, 0.79; 95% CI, 0.60-1.04; nominal P = .0493).2 The median OS in this population was 34.0 months in the dostarlimab arm and 27.0 months in the placebo arm. The estimated 24-month OS rates were 66.5% (95% CI, 59.2%-72.8%) and 53.2% (95% CI, 45.6%-60.2%), respectively.

The safety profile for dostarlimab plus carboplatin and paclitaxel was generally consistent with the known safety profiles of each drug, according to the news release.1 The most common treatment-emergent adverse effects in the dostarlimab arm included rash, maculopapular rash, pyrexia, hypothyroidism, increased aspartate aminotransferase levels, increased alanine aminotransferase levels, and dry skin.

In August 2024, the FDA expanded the indication for dostarlimab plus chemotherapy followed by dostarlimab monotherapy to include all adult patients with primary advanced or recurrent endometrial cancer.3

Part 2 of RUBY is ongoing and investigating dostarlimab plus carboplatin and paclitaxel followed by dostarlimab plus niraparib (Zejula) vs placebo plus carboplatin and paclitaxel followed by placebo alone in patients with primary advanced or recurrent endometrial cancer.1

References

1. European Commission expands Jemperli (dostarlimab) plus chemotherapy approval to all adult patients with primary advanced or recurrent endometrial cancer. News release. GSK. January 20, 2025. Accessed January 20, 2025. https://www.gsk.com/en-gb/media/press-releases/european-commission-expands-jemperli-dostarlimab-plus-chemotherapy-approval-to-all-adult-patients-with-primary-advanced-or-recurrent-endometrial-cancer/
2. 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 Aug;35(8):728-738. doi:10.1016/j.annonc.2024.05.546
3. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA. August 1, 2024. Accessed January 20, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy