March 27 2023
Protocol-specified first interim analysis results from the Phase III NRG-GY018 clinical trial comparing pembrolizumab combined with standard of care chemotherapy followed by maintenance pembrolizumab to placebo combined with chemotherapy followed by placebo indicated that patients with stage III-IV or recurrent endometrial cancer who received pembrolizumab exhibited improved progression-free survival outcomes. These findings were presented as a late-breaking abstract at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer and are also simultaneously being published in the New England Journal of Medicine.
NRG-GY018 accrued 816 women with stage III-IV or recurrent endometrial cancer, with two defined patient cohorts: mismatch repair deficient (dMMR) and mismatch repair proficient (pMMR). Patients on the trial were randomly assigned to receive pembrolizumab combined with carboplatin and paclitaxel (for a planned six, 3-week cycles), followed by pembrolizumab maintenance (for up to fourteen, 6-week cycles) on Arm A or placebo combined with carboplatin and paclitaxel, followed by placebo maintenance on Arm B.
In the pMMR cohort of 591 evaluable patients, after a median follow-up of 7.9 months, the pembrolizumab regimen significantly reduced the risk of disease progression or death by 46% (HR=0.54 [95% CI, 0.41-0.71]; p<0.00001) compared to chemotherapy alone; median PFS was 13.1 months (95% CI, 10.5-18.8) for the pembrolizumab regimen versus 8.7 months (95% CI, 8.4-10.7) for chemotherapy alone. In the dMMR cohort of 225 evaluable patients, after a median follow-up of 12 months, the pembrolizumab regimen significantly reduced the risk of disease progression or death by 70% (HR=0.30 [95% CI, 0.19-0.48]; p<0.00001) compared to chemotherapy alone; median PFS was not reached (95% CI, 30.6-NR) for the pembrolizumab regimen versus 7.6 months (95% CI, 6.4-9.9) for chemotherapy alone.
“Patients with advanced stage or recurrent endometrial cancer, the most common type of gynecologic cancer in the U.S., face a poor prognosis with limited treatment options,” stated Ramez Eskander, MD, of the University of California San Diego Moores Cancer Center and the Principal Investigator of the NRG-GY018 trial. “In this study, pembrolizumab in combination with carboplatin and paclitaxel resulted in a statistically significant and clinically meaningful improvement in PFS in both the dMMR and pMMR study populations. Future analysis will examine the secondary endpoints of this study, including overall survival and quality of life outcomes.”
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.
Citation
Eskander RN, Sill MW, Beffa L, Moore RG, Hope J, Musa FB, Mannel RS, Shahin MS, Cantuaria GH, Girda E, Mathews CA, Kavecansky J, Leath CA III, Gien LT, Hinchclilff EM, Lele SB, Landrum L, Backes F, O'Cearbhaill R, Liu R, Hill EK, Thaker P, John SV, Powell MA, Aghajanian C. Pembrolizumab (pembro) versus placebo in addition to carboplatin and paclitaxel (C+P) for measurable stage 3 or 4a, stage 4b or recurrent endometrial cancer (EC), the phase 3, NRG GY018 Study. SGO (Society of Gynecologic Oncology).
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to conduct clinical trials with emphasis on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.
www.nrgoncology.org