In a Japanese phase III trial (NINJA) reported in the Journal of Clinical Oncology, Hamanishi et al found that nivolumab did not improve overall survival vs chemotherapy with either gemcitabine or pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer.
Study Details
In the open-label multicenter trial, 316 patients who had received no more than one prior regimen after diagnosis of platinum resistance were randomly assigned to receive nivolumab at 240 mg every 2 weeks (n = 157) or investigator’s choice at enrollment of gemcitabine or pegylated liposomal doxorubicin (n = 159). Gemcitabine (n = 75) was given at 1,000 mg/m2 on days 1, 8, and 15 followed by a week off; pegylated liposomal doxorubicin (n = 84) was given at 50 mg/m2 once every 4 weeks. Treatment was continued until complete response, progressive disease, or unacceptable toxicity; nivolumab could be continued beyond disease progression. The primary endpoint was overall survival.
Overall and Progression-Free Survival
Median overall survival was 10.1 months (95% confidence interval [CI] = 8.3–14.1 months) in the nivolumab group vs 12.1 months (95% CI = 9.3–15.3 months) in the chemotherapy group (hazard ratio [HR] = 1.0, 95% CI = 0.8–1.3, P = .808). No difference was observed among 124 patients with PD-L1 tumor proportion score ≥ 1% (HR = 1.09, 95% CI = 0.73–1.64). Overall survival was numerically better with nivolumab among 67 patients with clear cell carcinoma (HR = 0.78, 95% CI = 0.46–1.32) and among 99 who received one chemotherapy regimen after platinum resistance diagnosis (HR = 0.74, 95% CI = 0.48–1.14).
KEY POINTS
- Nivolumab did not improve overall survival vs gemcitabine or pegylated liposomal doxorubicin.
- Progression-free survival was significantly poorer with nivolumab vs chemotherapy.
Median progression-free survival was 2.0 months (95% CI = 1.9–2.2 months) in the nivolumab group vs 3.8 months (95% CI = 3.6–4.2 months) in the chemotherapy group (HR = 1.5, 95% CI = 1.2–1.9, P = .002). Objective response was observed in 7.6% vs 13.2% of patients (odds ratio = 0.6, 95% CI = 0.2–1.3, P = .191). Median duration of response was 18.7 vs 7.4 months.
Adverse Events
Treatment-related adverse events of any grade were observed in 61.5% of patients in the nivolumab group vs 98.1% of the chemotherapy group. Grade 3 or 4 treatment-related adverse events occurred in 10.9% vs 65.2% of patients; the most common were anemia (2.6%) in the nivolumab group and decreased neutrophil count (40.0%) in the chemotherapy group. Treatment-related adverse events led to discontinuation of treatment in 7% vs 10% of patients.
The investigators concluded, “Although well-tolerated, nivolumab did not improve overall survival and showed worse progression-free survival compared with gemcitabine or pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer.”
Junzo Hamanishi, MD, PhD, of the Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The trial was supported by Ono Pharmaceutical Co, Ltd, and Bristol Myers Squibb Company. For full disclosures of the study authors, visit ascopubs.org.
