Nivolumab Demonstrates Efficacy in Platinum-Resistant Ovarian Cancer

The majority of women with advanced ovarian cancer who achieve remission after surgery and chemotherapy eventually relapse, and the current treatments for platinum-resistant and taxane-resistant ovarian tumors fail to demonstrate adequate antitumor effects. Poor prognosis in ovarian cancer is associated with expression of programmed cell death-1 (PD-1) ligand 1 (PD-L1), which binds to PD-1 receptors on T cells to suppress host antitumor immunity. Hamanishi and colleagues conducted a single-center, open-label, phase II clinical trial to evaluate the safety and efficacy of nivolumab, an anti–PD-1 monoclonal antibody that blocks PD-1/PD-L1 signaling, in 20 patients with advanced or relapsed platinum-resistant ovarian cancer. Patients received nivolumab at a dose of either 1 mg/kg or 3 mg/kg every 2 weeks for 1 year or until disease progression occurred. The best overall response rate across both cohorts was 15% (3 of 20 patients), with response rates of 10% in the low-dose cohort and 20% in the high-dose cohort. In the low-dose cohort, one patient achieved a partial response and four patients had stable disease; in the high-dose cohort, two patients experienced a complete and durable response. Across the two cohorts, the disease control rate was 45%, the median progression-free survival time was 3.5 months, and the median overall survival time was 20.0 months. Of note, tumor expression of PD-L1 did not significantly correlate with objective response. Tolerability was similar for both dosage cohorts, with 8 (40%) of 20 patients experiencing grade 3 or 4 treatment-related adverse events and the most common adverse events relating to thyroid function. Overall, these results demonstrate the clinical efficacy and tolerability of nivolumab for patients with advanced or relapsed platinum-resistant ovarian cancer and provide a rationale for larger-scale clinical trials of nivolumab for platinum-resistant ovarian cancer or other cancers that escape host immunity via PD-1/PD-L1 signaling.

Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, et al. Safety and antitumor activity of anti–PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol 2015 Sep 8 [Epub ahead of print].