In a phase II NRG Oncology trial (NRG GY003) reported in the Journal of Clinical Oncology, Dmitriy Zamarin, MD, PhD, and colleagues found that the addition of ipilimumab to nivolumab improved objective response rate and progression-free survival in women with persistent or recurrent epithelial ovarian cancer.

Dmitriy Zamarin, MD, PhD

Study Details

In the open-label multicenter trial, 100 patients were randomly assigned between June 2015 and August 2017 to receive nivolumab plus ipilimumab (n = 51) or nivolumab alone (n = 49). Patients had to have measurable disease, have received one to three prior treatment regimens, and have a platinum-free interval < 12 months.

The nivolumab group received nivolumab at 3 mg/kg every 2 weeks; the nivolumab/ipilimumab group received nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg every 3 weeks. After induction, both groups received nivolumab at 3 mg/kg every 2 weeks for a maximum of 42 doses.

Responses and Progression-Free Survival

Objective responses during the first 6 months of treatment were observed in 16 patients (31.4%; 3 with complete response) in the nivolumab/ipilimumab group vs 6 patients (12.2%; 3 with compete response) in the nivolumab group (odds ratio = 3.28, P = .034). Programmed cell death ligand 1 expression was not significantly associated with response in either group.

Response durations ≥ 6 months were observed in eight vs four responders. An additional 20 (39%) and 14 (29%) patients had stable disease.

Median progression-free survival was 3.9 months in the nivolumab/ipilimumab group vs 2.0 months in the nivolumab-alone group (hazard ratio [HR] = 0.528, P = .004), with 6-month rates of 25.5% vs 16.3%. Median overall survival was 28.1 vs 21.8 months (HR = 0.79, P = .43).

Adverse Events

Grade ≥ 3 treatment-related adverse events occurred in 49% of patients in the nivolumab/ipilimumab group vs 33% of the nivolumab alone group, with the most common in the combination group being asymptomatic elevation in pancreatic enzymes (16%), elevation in liver enzymes (8%), anemia (8%), and colitis or diarrhea (6%). Among grade 2 to 4 treatment-related adverse events, the nivolumab/ipilimumab group had numerically higher rates of colitis or diarrhea (16% vs 4%, P = .09), anemia with or without hemolysis (16% vs 4%, P =.09), and rash (14% vs 4%, P = .16). No treatment-related deaths were reported.

The investigators concluded, “Compared with nivolumab alone, the combination of nivolumab and ipilimumab in [patients with] epithelial ovarian cancer resulted in superior response rate and longer, albeit limited, progression-free survival, with toxicity of the combination regimen comparable to prior reports. Additional combination studies to enhance durability of the dual regimen are warranted.”

Dr. Zamarin, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Cancer Institute, with Bristol-Myers Squibb as the Cooperative Research and Development Agreement collaborator. For full disclosures of the study authors, visit ascopubs.org.