Addition of a CTLA-4–Targeted Therapy to a Checkpoint Inhibitor in Ovarian Cancer

Key Points

  • Within 6 months of randomization, 6 (12.2%) responses occurred in the treatment arm receiving nivolumab alone, and 16 (31.4%) responses occurred in the arm receiving nivolumab plus ipilimumab followed by nivolumab maintenance. Following the 6-month evaluation period, 1 additional response appeared in the combination arm.
  • The platinum-free interval stratified HR for progression-free survival was 0.528, and the respective HR for death was 0.789.
  • Adverse events (grade 3 or higher) were more prevalent in the combination arm; however, there were no new safety signals and no treatment-related deaths.

An analysis of the NRG Oncology clinical trial NRG-GY003 suggests that adding ipilimumab (Yervoy), a monoclonal antibody that targets the protein receptor cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), to a regimen with the checkpoint inhibitor nivolumab (Opdivo) could improve response and progression-free survival for women with recurrent epithelial ovarian cancer. These results were presented at the 17th Biennial Meeting of the International Gynecologic Cancer Society in Kyoto, Japan.

NRG-GY003 assessed the difference in tumor response proportions in 100 women between two treatment regimens over a period of 6 months. Participants on this trial were randomly assigned to either the first treatment arm (TA1), which received nivolumab alone, or the second arm (TA2), which received a combination of ipilimumab and nivolumab followed by maintenance nivolumab. Tumor response proportions were evaluated through Response Evaluation Criteria in Solid Tumors, version 1.1, and secondary analyses included progression-free survival, overall survival, and adverse events.

Study Results

Within 6 months of randomization, 6 (12.2%) responses occurred in TA1 and 16 (31.4%) responses occurred in TA2 (odds ratio [OR] = 3.28, 85% confidence interval [CI] > 1.90). Following the 6-month evaluation period, one additional response appeared on TA2. The platinum-free interval stratified hazard ratio (HR) for progression-free survival was 0.528 (95% CI = 0.339–0.821), and the respective hazard ratio for death was 0.789 (95% CI = 0.439–1.418).

Adverse events (grade 3 or higher) were more prevalent in TA2. However, there were no new safety signals and no treatment-related deaths.

“From my perspective, this is the first evidence that the addition of CTLA-4–targeted therapy to programmed cell death protein 1 (PD-1)–targeted therapy in patients with ovarian cancer may be more beneficial than PD-1–targeted therapy alone. Future directions could include a trial combining nivolumab and ipilimumab in front-line therapy as an adjunct to standard chemotherapy,” stated Robert A. Burger, MD, the study’s lead author and Professor of Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania.

The trial was not powered to detect a difference in overall survival. There was no preliminary evidence to indicate a detrimental effect from TA2.

This trial was sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI), and the agents were provided to NCI by Bristol-Myers Squibb under the cooperative research and development agreements between Bristol-Myers Squibb and NCI for the development of nivolumab and ipilimumab.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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