Updated overall survival analysis and examination of subsequent therapy in endometrial cancer (EC) patients (pts) treated with pembrolizumab plus carboplatin/paclitaxel (CP) as compared to CP plus placebo (PBO) in the NRG-GY018 trial.

Abstract

5502 Background: NRG-GY018, the only phase 3 trial examining dMMR and pMMR EC populations independently, identified a 70% and 46% reduction in the risk of disease progression or death in advanced stage or recurrent dMMR and pMMR EC patients treated with pembrolizumab plus CP. Here we report on updated overall survival and post-study immune checkpoint inhibition (ICI) therapy. Methods: 810 pts were randomized 1:1 to pembrolizumab + CP or PBO + CP Q3W for 6 cycles followed by maintenance pembrolizumab or PBO Q6W for up to 24 months. Updated OS analysis data cut off was December 23, 2025, with information fraction of 42% and 78% in the dMMR and pMMR EC cohorts, respectively. Median follow up in the dMMR cohort was 44.6 months (95% CI 42.5 to 46.8) and 40.1 months (95% CI 38.9 to 42.2) in the pMMR cohorts. Study sites were queried to abstract data regarding start and end date of post study ICI use. Results: The addition of pembrolizumab resulted in a sustained OS benefit in the dMMR EC cohort. At 48-month landmark assessment, 80% of the pembrolizumab treated dMMR EC patients were alive, versus 60% of those treated with placebo, HR 0.53 (95% CI 0.32 to 0.89). This survival advantage was maintained despite at least 55% (n=62) of dMMR EC patients in the placebo arm receiving post study ICI. In the pMMR EC population, with an information fraction of 78%, the median OS in the pMMR cohort treated with pembrolizumab was 46.9 months versus 35.1 months for those receiving placebo, HR 0.84 (95% CI 0.66 to 1.06). This benefit was maintained despite at least 57% (n=167) pMMR EC patients in the placebo arm receiving post study ICI (most commonly lenvatinib plus pembrolizumab). In the pMMR EC cohort, 70 patients in the pembrolizumab arm and 167 patients in the placebo arm received post study ICI, with the median duration of treatment of 6.2 months in both populations. Conclusions: In the NRG GY018 study, with prolonged follow up, the addition of pembrolizumab to CP resulted in a sustained OS benefit despite substantial post study ICI use. In the pMMR population, an 11.8 month OS advantage was observed, despite at least 57% of the placebo patients receiving post study ICI. This data further supports the current US FDA approved indication of this regimen in the treatment of advanced stage or recurrent endometrial cancer irrespective of MMR status. Clinical trial information: NCT03914612 .