The Addition of CTLA4 to PD-1 Precision Therapy Could Benefit Women with Ovarian Cancer
by Dr. C.H. Weaver M.D. 10/2018
Analysis of the NRG Oncology clinical trial NRG-GY003 suggests that combining Yervoy (ipilimumab), a monoclonal antibody that targets the protein receptor CTLA-4, with the checkpoint inhibitor Opdivo (nivolumab) could improve the treatment for women with recurrent epithelial ovarian cancer.
Opdivo blocks the activity of a molecule PD-1 found on T cells and is approved for advanced non-small cell lung cancer, melanoma, and renal cell carcinoma patients. Yervoy targets a molecule called CTLA-4 on T cells and is approved for advanced melanoma patients. Studies have shown that Opdivo combined with Yervoy results in improved antitumor activity when compared to either agent alone. Doctors from Dana Farber Cancer Institute in Boston MA have reported similar observations in the treatment of malignant melanoma further supporting the idea that this combination precision cancer immunotherapy is promising.(2)
The NRG-GY003 enrolled 100 women with recurrent epithelial ovarian cancer and treated half with Opdivo and half with Opdivo plus Yervoy followed by maintenance Opdivo. When evaluated ~ 6 months from initiation of treatment, three times as many patients treated with the combination had responded to treatment. Overall ~12% of Opdivo treated patients responded compared to ~ 35% of those receiving Opdivo combined with the CTLA-4 blocker, Yervoy.
According to Dr. Robert Burger M.D. Professor of Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania “this is the first evidence that the addition of CTLA4 targeted therapy to PD-1 targeted therapy in patients with ovarian cancer may be more beneficial than PD-1 targeted therapy alone.” Larger trials will need to be performed to confirm these observations and the true benefit of such a combination will most likely be realized if the drug combination is used earlier in the disease course.
Burger RA, Sill M, Zamarin D, Powell D, Frak I, Zivanovic O, Gunderson C, Ko E, Matthews C, Sharma S, Hagemann A, Khleif S, Aghajanian C. (2018, September). NRG Oncology Phase II Randomized Trial of Nivolumab with or without Ipilimumab in Patients with Persistent or Recurrent Ovarian Cancer. Abstract presented at the Biennial Meeting of the International Gynecologic Cancer Society (IGCS), Kyoto, JP.