The trial, sponsored by the National Cancer Institute, also showed that the combination significantly extends the time to disease progression or death. A trend toward better survival rates was seen, but the trial was not powered to detect significant differences in this outcome.
The findings were recently presented at the 17th Biennial Meeting of the International Gynecological Cancer Society (IGCS) in Kyoto, Japan. The research was titled “NRG Oncology Phase II Randomized Trial of Nivolumab with or without Ipilimumab in Patients with Persistent or Recurrent Ovarian Cancer.”
Immune checkpoint inhibitors, or medicines that boost the immune system to attack cancer cells more efficiently, have been at the forefront of cancer treatment for the past five years.
These medicines are approved for multiple cancer types, including melanoma, lung cancer, head and neck cancer, kidney cancer, and bladder cancer. But to date, no immune checkpoint inhibitor has been approved for ovarian cancer patients.
Opdivo, a medicine that blocks the interaction of PD-1 with its ligands PD-L1 and PD-L2, has shown promise in patients with advanced ovarian cancer who are resistant to platinum-based chemotherapy. In a Phase 2 trial, 15 percent of patients responded to treatment, and patients lived for a median of 3.5 months without their tumor progressing.
Now, researchers set out to investigate whether adding Yervoy to Opdivo could bring additional benefits to these patients.
The study, called NRG-GY003 (NCT02498600), included 100 patients with cancers in the ovaries, fallopian tube, or peritoneum — a membrane lining the abdominal cavity and covering the abdominal organs — who had failed to respond to at least one prior therapy.
Its primary objective was to determine whether more patients receiving the combination responded to their treatment. Secondary outcomes included the time to disease progression or death, overall survival, and safety.
Patients received either Opdivo alone or a combination of Opdivo and Yervoy, both followed by Opdivo maintenance.
In the first six months of treatment, 31.4 percent of patients receiving the combination achieved at least a partial tumor reduction, while this was only observed in 12.2 percent of patients on Opdivo. Researchers reported one additional response in the combination group after six months from enrollment.
The combination also reduced the risk of disease progression or death by 47 percent, and showed a trend toward increased survival.
While more patients on the combination group experienced serious or worse adverse events, safety was consistent with prior studies of Opdivo and Yervoy. No treatment-related deaths were reported.
“From my perspective, this is the first evidence that the addition of CTLA4 targeted therapy [Yervoy] to PD-1 targeted therapy [Opdivo] in patients with ovarian cancer may be more beneficial than PD-1 targeted therapy alone,” Robert A. Burger, MD, the study’s lead author, said in a press release.
“Future directions could include a trial combining nivolumab and ipilimumab in front-line therapy as an adjunct to standard chemotherapy,” said Burger, a professor of obstetrics and gynecology at the Perelman School of Medicine at the University of Pennsylvania.