Contemporary upfront management of endometrial cancer: the role of first-line immunotherapy

In this in-depth interview, Dr Laure-Anne Teuwen speaks with Dr Justine Himpe about the evolving first-line management of advanced or recurrent endometrial cancer, with a focus on the RUBY and NRG-GY018 trials presented at ASCO 2026. Both studies evaluated the addition of immune checkpoint inhibition to carboplatin-paclitaxel chemotherapy, followed by maintenance immunotherapy, and together support the move towards immunotherapy-based first-line treatment in this setting.

The first study highlighted was the RUBY trial, a phase III investigation evaluating dostarlimab in combination with chemotherapy versus chemotherapy alone in patients with advanced or recurrent endometrial cancer.¹ Investigators presented long-term survival outcomes and mixture cure modelling analyses focused on the mismatch repair-deficient (dMMR) population. At a median follow-up of 55.6 months, the benefit remained very robust: only four additional progression events occurred compared with the prior report, and the progression-free survival (PFS) showed a clear plateau. A sustained overall survival (OS) benefit was also observed. The four-year PFS rate was 58% with dostarlimab plus chemotherapy versus 16% with chemotherapy alone, while the four-year OS rate was 73% versus 40%, respectively. Additional analyses, including conditional survival and a mixture cure model, suggested that patients who remain progression-free after the first years of treatment may have a high probability of long-term disease control. The mixture cure model estimated a potential cure fraction of 54% with dostarlimab plus chemotherapy, compared with 14% in the control arm, although these exploratory results should be interpreted cautiously because of the small sample size.

A second important update in endometrial cancer came from NRG-GY018, the pivotal phase III trial evaluating pembrolizumab combined with chemotherapy in the first-line treatment of advanced disease.² Updated OS analyses were presented separately for patients with dMMR and proficient mismatch repair (pMMR) tumours. In the dMMR subgroup, the OS benefit was sustained at longer follow-up (median follow-up 49 months), although the data remain relatively immature. At the four-year landmark analysis, 79% of patients receiving pembrolizumab plus chemotherapy remained alive compared with 60% of those treated with chemotherapy alone (HR[95% CI]: 0.56[0.34-0.92]). Median OS was not reached in either arm. In the pMMR subgroup, the OS improvement was not statistically significant, but a clinically meaningful difference of around nine months was observed (median OS: 44.4 vs 35.1 months; HR[95% CI]: 0.86[0.69-1.08]). An important point discussed in the interview was the high use of post-progression immunotherapy in the control arm of NRG-GY018, which may partly explain differences in hazard ratios between trials and may have reduced the apparent survival benefit of first-line pembrolizumab.

Finally, the interview highlights the heterogeneity of pMMR endometrial cancer. Current data do not yet clearly identify subgroups that can safely omit immunotherapy, but future studies may refine treatment selection according to molecular features such as TP53 status, histology, measurable disease and prior treatment exposure. Overall, the discussion reinforces the importance of introducing immunotherapy early, especially in dMMR advanced endometrial cancer, while continuing to personalise strategies for the more heterogeneous pMMR population.