Nivolumab Combo Yields Better Response Than Monotherapy in Epithelial Ovarian Cancer

Findings from a study of patients with epithelial ovarian cancer showed that nivolumab plus ipilimumab yields a greater response rate and longer progression-free survival than nivolumab monotherapy (J Clin Oncol. 2020 Apr 10. Epub ahead of print).

In an interview with Oncology Learning Network, lead investigator Dmitriy Zamarin, MD, PhD, Assistant Attending Physician and Translational Research Director, Gynecologic Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, spoke about the background and clinical significance of these results.

What existing data led you and your co-investigators to conduct this research?

Prior studies of single agent PD-1 or PD-L1 inhibitors demonstrated limited activity in ovarian cancer. Based on the emerging data from other cancers, we hypothesized that a combination of CTLA-4 blockade with PD-1 blockade in ovarian cancer could result in superior efficacy.

Please briefly describe your study and its findings. Were any of the outcomes particularly surprising?

This was a National Cancer Institute–sponsored randomized phase 2 trial conducted by the NRG. The study compared single agent nivolumab with a combination of nivolumab and ipilimumab, for 4 doses, followed by nivolumab maintenance, and enrolled 50 patients per arm.

Combination therapy resulted in higher incidence of treatment-related adverse events, although this was comparable to other studies with this combination and most of the patients were able to complete all assigned combination treatments.

Treatment combination resulted in significant increase in the overall response rate, with 12% response rate observed in the single-agent nivolumab arm compared to 31.4% response rate in the combination arm. There was also a statistically significant increase in the median progression free survival, although the increase was limited to 1.9 months.

What are the possible real-world applications of these findings in clinical practice?

The study indicates that combined immune checkpoint blockade is likely to be more effective in therapy of ovarian cancer, but the limited durability of the response highlights that this combination might not be ready for real-world application.

Further research into the combination, perhaps by combining it with additional agents, can hopefully establish a setting where such treatment could extend the benefit from immunotherapy to ovarian cancer patients.

Do you and your co-investigators intend to expand upon this research?

As mentioned above, we are initiating some studies exploring combinations of CTLA-4 and PD-1 blockade with chemotherapy. We are hopeful that through the use of these different modalities we will be able to improve both response rate as well as durability of benefit from these treatments.

Is there anything else you would like to add?

The study also highlighted that PD-L1 expression, which was found to be predictive of response in other cancer types, was not associated with response in this study. This finding highlights that at present we still don’t have a valid biomarker of response to immunotherapy in ovarian cancer and stresses the rationale for identification of other biomarkers that would be applicable to this cancer.