Pembrolizumab combination therapy improves survival in recurrent endometrial cancer patients

Previously, immature overall survival results of the NRG Oncology GY018 (NRG-GY018) trial suggested that the use of the immunotherapy drug pembrolizumab in combination with chemotherapy improved overall survival for patients with advanced stage or recurrent endometrial cancer when compared to chemotherapy alone. Notably, this benefit was observed in both the mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR) populations. An analysis of the study data, with prolonged follow-up, demonstrated that there was a sustained numerical benefit in overall survival for patients who received pembrolizumab with chemotherapy even when a large proportion of the initial placebo treated patients received post-protocol immunotherapy. These results were presented during the Gynecologic Oncology Session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.

These findings are particularly important because they address a long-standing gap in the treatment of advanced and recurrent endometrial cancer which historically has been plagued by poor outcomes and limited therapeutic progress. The fact that the survival advantage persisted in the dMMR and pMMR EC populations, adds great confidence to the use pembrolizumab in combination with chemotherapy in treatment of appropriately selected patients, irrespective of MMR status. In the pMMR EC cohort, the persistent non-statistically significant but notable benefit in overall survival, despite substantial post study immunotherapy utilization, may suggest that early incorporation of this regimen provides greatest clinical benefit."

Ramez N. Eskander, MD, of the University of California, San Diego and lead author of the NRG-GY018 abstract

Despite the change in treatment for the patients on the reference arm of this study, patients that initially received pembrolizumab and chemotherapy on the experimental arm among the pMMR group still experienced a 9.3-month median overall survival benefit in the prolonged follow-up analysis.

Patients on NRG-GY018 randomly assigned 809 patients to receive either pembrolizumab or placebo with carboplatin and paclitaxel chemotherapy. Overall survival analysis data were cut off on April 14, 2026, with information fraction of 43% and 82% in the dMMR and pMMR EC cohorts, respectively.

In the prolonged follow-up, the addition of pembrolizumab resulted in a sustained overall survival benefit in the dMMR endometrial cancer cohort. At 48 months, 79% of the dMMR patients treated with pembrolizumab were alive versus 60% of the patients treated with placebo, HR 0.56 (95% CI 0.34 to 0.92). This benefit continued despite at least 93% of dMMR endometrial cancer patients in the control arm, who received subsequent treatment, receiving post-study immunotherapy. In the pMMR population, the median overall survival was 44.4 months versus 35.1 months for the patients receiving placebo. Again, the survival benefit continued despite at least 81% of pMMR endometrial cancer patients in the control arm receiving post-study immunotherapy.

This project was supported by the NRG Oncology Operations grant U10CA180868 and the NRG Oncology SDMC grant U10CA180822 from the National Cancer Institute (NCI), part of the National Institutes of Health and conducted by the NCI National Clinical Trials Network. Funding and support were also received from Merck & Co., Inc. through a Cooperative Research and Developmental Agreement with NCI. NRG-GY018 was conducted with funding supplemental to the CRADA from Merck in an Agreement between Merck and The GOG Foundation d/b/a NRG Oncology Philadelphia East.