Results from the NRG Oncology phase I clinical trial NRG-GOG 9929 show that utilizing the immunotherapy drug ipilimumab after chemoradiotherapy (CRT) is tolerated in the curative treatment of women with lymph node-positive cervical cancer. The maximum tolerated dose of ipilimumab was determined to be 10 mg/kg. These results are published in JAMA Oncology and was be highlighted at a gynecologic session during the American Society for Radiation Oncology's (ASTRO) Annual Meeting in September 2019.
NRG-GOG 9929 is the first trial to describe the safety of immunotherapy following CRT in curative cervical cancer. Currently, many women with node-positive cervical cancer who are treated with CRT will recur. Therein lies the need to develop a safe and effective therapeutic strategy, such as the use of immunotherapy, to improve outcomes for women with this type of cancer. NRG-GOG 9929 was designed to primarily determine the safety and proper dosage of ipilimumab (immunotherapy) following the standard CRT treatment; however, a secondary endpoint included in the trial was measuring survival outcomes.
Twenty-one patients on NRG-GOG 9929 received CRT followed by ipilimumab (immunotherapy). Patients received one of two potential dose levels, 3mg/kg (DL1) and 10mg/kg (DL2), in order to determine the maximum dose of immunotherapy. Only 2 patients experienced self-limited grade 3 toxicities. The 12-month progression free survival rate was 81% and the 12-month overall survival rate was 90%. All patients completed CRT, 86% of women completed 4 cycles of ipilimumab, and 14% of women completed 2 cycles of ipilimumab. PD-1 expression increased with CRT and was sustained with immunotherapy.
"Future researchers should consider the findings of this prospective phase 1 trial when developing clinical trials for women with node-positive cervical cancer. We need to have more studies and investigations that will help to identify therapeutic targets to improve outcomes in this patient population," stated Jyoti S. Mayadev, MD, of University of California San Diego School of Medicine and lead author of NRG-GOG 9929.
This study was supported by National Cancer Institute (NCI) grants to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517), the GOG Tissue Bank (CA 114793), NRG Oncology (one U10 CA180822), the NRG Oncology Biospecimen Bank-Columbus (CA 196067), and NRG Oncology Operations (U10CA180868). Translational research was supported by grants from the University of Southern California Norris Comprehensive Cancer Center Women's Auxiliary Club , Cancer Research Institute Clinic and Laboratory Integration , the University of Southern California Norris Comprehensive Cancer Center Immune Monitoring Core Facility and the National Cancer Institute Cancer Center Shared Grant Award P30CA014089 (Drs. Diane DaSilva, Ph.D. and Yvonne G. Lin, M.D.). Bristol-Myers-Squibb (BMS) supplied ipilimumab for the study which was conducted under a Clinical Trials Agreement (CTA) between NCI and BMS.
Mayadev JS, Enserro D, Lin YG, Da Silva DM, Lankes HA, Aghajanian C, Ghamande S, Moore KN, Kennedy VA, Fracasso PM, Schilder RJ. Sequential Ipilimumab After Chemoradiotherapy in Curative-Intent Treatment of Patients With Node-Positive Cervical Cancer. JAMA Oncol. Nov. 27, 2019. doi: 10.1001/jamaoncol.2019.3857. [Epub ahead of print]
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 carry out clinical trials with emphases 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. http://www.