Previously, preliminary overall survival results from the NRG Oncology GY018 (NRG-GY018) trial suggested that the immunotherapy drug pembrolizumab, when combined with chemotherapy, improved overall survival for patients with advanced or recurrent endometrial cancer compared to chemotherapy alone. Remarkably, this benefit was observed in both mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR) populations. Analysis of study data with long-term follow-up demonstrated a sustained numerical benefit in overall survival for patients who received chemotherapy and pembrolizumab, even when the majority of initially placebo-treated patients received post-protocol immunotherapy. These results were presented at 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 has historically suffered from poor prognosis and limited treatment advances. The fact that the survival benefit persisted in the dMMR and pMMR EC populations provides great confidence in the use of pembrolizumab in combination with chemotherapy in the treatment of appropriately selected patients, regardless of MMR status. In the pMMR EC cohort, despite significant post-study use of immunotherapy, the sustained non-statistically significant but notable benefit in overall survival may suggest that early introduction of this regimen provides the greatest clinical benefit. ”
Ramez N. Eskander, MD, University of California, San Diego, first author of NRG-GY018 abstract
Despite changes in treatment for patients in the study’s reference group, patients in the pMMR group who first received pembrolizumab and chemotherapy in the experimental group still experienced a median overall survival benefit of 9.3 months in the long-term follow-up analysis.
NRG-GY018 randomly assigned 809 patients to receive pembrolizumab or placebo with carboplatin and paclitaxel chemotherapy. Overall survival analysis data were censored on April 14, 2026, and the information rates for the dMMR EC and pMMR EC cohorts were 43% and 82%, respectively.
At long-term follow-up, the addition of pembrolizumab provided a sustained overall survival benefit in the dMMR endometrial cancer cohort. At 48 months, 79% of dMMR patients treated with pembrolizumab were alive compared with 60% of patients treated with placebo, HR 0.56 (95% CI 0.34 to 0.92). This benefit continued even though at least 93% of dMMR endometrial cancer patients in the control group received subsequent treatment and post-study immunotherapy. In the pMMR population, median overall survival was 44.4 months compared to 35.1 months for patients who received placebo. Again, the survival benefit continued even though at least 81% of pMMR endometrial cancer patients in the control group received post-study immunotherapy.
This project was supported by NRG Oncology Operating Grant U10CA180868 and NRG Oncology SDMC Grant U10CA180822 from the National Cancer Institute (NCI), part of the National Institutes of Health, and was conducted by the NCI National Clinical Trials Network. Funding and support was also received from Merck & Co., Inc. through a joint research and development agreement with NCI. NRG-GY018 was conducted under an agreement between Merck and the GOG Foundation (NRG Oncology Philadelphia East) with supplemental funding to CRADA from Merck.
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Reference magazines:
Eskander, RN; Others. (2026) Pembrolizumab and chemotherapy in advanced or recurrent endometrial cancer: Updated exploratory analysis of overall survival and post-study response to immune checkpoint inhibition in the NRG GY018 phase 3 randomized trial. This paper was presented at the Gynecologic Oncology Session of the American Society of Clinical Oncology Annual Meeting. Chicago, Illinois. (May 2026).
