Dr Girda on the Use of Pembrolizumab Plus Chemotherapy in Endometrial Cancer

Eugenia Girda, MD, FACOG, gynecologic oncologist, Rutgers Cancer Institute, assistant professor, Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, discusses the use of pembrolizumab (Keytruda) plus chemotherapy for patients with endometrial cancer as seen in the phase 3 NRG-GY018 trial (NCT03914612). 

NRG-GY018 compared the use of pembrolizumab plus standard-of-care (SOC) paclitaxel and carboplatin with placebo plus chemotherapy in women with stage III to IV or recurrent endometrial cancer. The trial accrued 816 patients and stratified them according to mismatch repair–deficient (dMMR) or mismatch repair–proficient (pMMR) status. These patients were then randomly assigned to receive 6, 3-week cycles of pembrolizumab or placebo, plus chemotherapy followed by up to 14, 6-week cycles of maintenance pembrolizumab or placebo.

A prespecified interim analysis of the trial was presented at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer. Results showed that patients who received the pembrolizumab combination achieved a statistically significant and clinically meaningful improvement in median progression-free survival (PFS) in both study populations, Girda states.

Median PFS was not reached for patients in the dMMR cohort who received the pembrolizumab regimen, she reports. Comparatively, median PFS was 7.6 months in the placebo arm. Notably, the hazard ratio (HR) was 0.30, with a P value of less than .001, indicating a 70% reduction in the risk of disease progression or death in the pembrolizumab arm. In the pMMR cohort, patients also achieved a median PFS of 13.1 months with pembrolizumab vs 8.7 months with placebo. The HR was 0.54, with a P value of less than .001. The risk of death or disease progression in this cohort was reduced by 46%.

Further subgroup analysis showed benefit with the pembrolizumab regimen was seen regardless of whether patients had prior radiation therapy, adjuvant chemotherapy, newly diagnosed or advanced disease, or different histologies, Girda adds.

Overall, this trial has shifted the SOC in endometrial cancer by showing that pembrolizumab should be added to chemotherapy in all patients regardless of MMR status, Girda concludes.