Pembrolizumab Plus Chemotherapy Shows Sustained Survival in Advanced EC

The addition of pembrolizumab (Keytruda) to carboplatin and paclitaxel (CP) sustained overall survival (OS) benefits vs placebo and chemotherapy for patients with advanced or recurrent endometrial cancer, according to a presentation of long-term survival findings from the phase 3 NRG-GY018 trial (NCT03914612) given at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.

These findings aimed to provide longitudinal data on OS and the influence of subsequent therapies following the previous demonstration of statistically significant progression-free survival (PFS) benefits in this patient population regardless of mismatch repair status.

Main data

With a prolonged median follow-up of 49 months in the deficient mismatch repair (dMMR) cohort and 44 months in the mismatch repair proficient (pMMR) cohort, the pembrolizumab plus chemotherapy regimen followed by pembrolizumab maintenance provided a sustained survival benefit compared with chemotherapy alone. In the dMMR cohort, the hazard ratio (HR) for overall survival was 0.56 (95% CI, 0.34–0.92). The median OS was not reached (NR) in the pembrolizumab arm or the placebo arm. The 48-month OS rate was 78.6% (95% CI, 69.6%–85.2%) for the pembrolizumab group compared with 60.4% (95% CI, 50.0%–69.2%) for those who received placebo and chemotherapy.

In the mismatch repair proficient (pMMR) cohort, the addition of pembrolizumab showed a directionally favorable OS with an HR of 0.86 (95% CI, 0.69–1.08). The median OS was 44.4 months (95% CI, 37.8–52.1) in the pembrolizumab arm vs 35.1 months (95% CI, 30.2–43.8) in the placebo arm. The 48-month OS rates were 46.7% (95% CI, 40.0%–53.1%) and 39.5% (95% CI, 33.0%–46.0%), respectively.

Notably, these OS benefits persisted despite substantial use of poststudy immune checkpoint inhibitors (ICI) in the control arms. In the dMMR cohort, 93.2% of patients in the control arm who received poststudy therapy were treated with an ICI. Among these patients, 63.5% received ICI monotherapy and 17.6% received the combination of lenvatinib and pembrolizumab. In the pMMR cohort, 81.1% of patients in the control arm receiving poststudy therapy were treated with an ICI.

Trial details

The NRG-GY018 study enrolled 810 patients with endometrial cancer and randomly assigned them to receive: placebo every 3 weeks plus paclitaxel at 175 mg/m² and carboplatin at AUC 5 for 6 cycles, followed by placebo every 6 weeks for up to 14 additional cycles; or pembrolizumab 200 mg every 3 weeks plus the same chemotherapy regimen for 6 cycles, followed by pembrolizumab 400 mg every 6 weeks for up to 14 additional cycles. Stratification factors included MMR status, ECOG performance status, and prior adjuvant chemotherapy.

Patient Characteristics

The trial included 222 patients in the mismatch repair deficient (dMMR) cohort and 588 patients in the pMMR cohort. Those enrolled on the study had measurable stage III/IVA, or measurable/non-measurable stage IVB or recurrent endometrial cancer. Additionally, patients were required to have an institutional pathology report showing MMR results and an ECOG performance status of 0 to 2. Those with prior chemotherapy were excluded unless it was adjuvant therapy completed at least 12 months before study entry.

Main end points

The primary end point of NRG-GY018 was PFS as determined by investigator review per RECIST v1.1 guidelines in the dMMR and pMMR cohorts. The current analysis focused on updated secondary end points, specifically OS in the dMMR and pMMR cohorts and the administration of poststudy ICI therapy. OS was a pre-planned secondary end point, although it was not subject to a multiplicity strategy or alpha allocation in this analysis.

Safety

The safety profile observed in the NRG-GY018 trial remained consistent with the previously established profiles of the individual study agents. Adverse effects reported during the long-term follow-up did not reveal new safety signals beyond what was already known for pembrolizumab, carboplatin, and paclitaxel. The investigators noted that the findings supported the existing FDA and EMA approvals of the pembrolizumab regimen for the treatment of advanced or recurrent endometrial cancer regardless of MMR status.

Reference

Eskander RM, Sill M, Beffa L, et al. Updated overall survival analysis and examination of subsequent therapy in endometrial cancer (EC) participants treated with pembrolizumab plus carboplatin/paclitaxel (CP) as compared to CP plus placebo in the NRG-GY018 trial. J Clin Oncol. 2026;44(suppl 16):5502. doi:10.1200/JCO.2026.44.16_suppl.5502