Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)

Purpose: Patients with persistent/recurrent cervical cancer following platinum-based chemotherapy have limited therapeutic options. The Gynecologic-Oncology-Group conducted a phase II trial to assess efficacy and tolerability of nivolumab, an immune checkpoint inhibitor, in persistent/recurrent cervical carcinoma. Patients and methods: Key eligibility criteria included persistent/recurrent cervical cancer, failure of prior systemic therapy and ECOG PS 0-1. Nivolumab 3 mg/kg was given IV every 2 wk. until disease progression or intolerable toxicity. Response was assessed every 8 wk. for 6 months and every 12 wk. thereafter. The primary endpoints were objective response as assessed by RECIST 1.1. The study used a 2-stage group sequential design. PD-L1 expression was evaluated in tumor specimens by immunohistochemistry (IHC) using a combined-positive-score (CPS) cutoff of ≥1%. Results: Of 26 enrolled patients with persistent/recurrent cervical cancer, 25 were evaluable for response/toxicity with a median age of 45. 36% had ECOG PS of 1, and 100% had received one prior systemic chemotherapy regimen. PD-L1 expression (≥1%) was identified in 77.3% of tumor samples. As of 03/05/19, all patients were off study treatment; median follow-up for survival status was 32 months (range, 2–41.5). There were 21 (84%) patients with a treatment-related adverse event (TRAE) and most were grades 1–2. Six (24%) patients had grade 3 TRAEs with 1 discontinuing nivolumab due to hepatic toxicity. No grade 5 TRAEs occurred, and 2 patients had grade 4 TRAEs. One confirmed partial response (4%; 90% CI, 0.4%–22.9%), duration of response 3.8 months. Thirty-six percent of patients had stable disease (SD) (9/25; 90% CI, 20.2%–54.4%); the median duration of SD was 5.7 months (range, 3.5–12.7). Estimated PFS and OS at 6 months were 16% and 78.4%, respectively. Conclusion: Single agent nivolumab exhibited low antitumor activity and an acceptable safety profile in patients with persistent/recurrent cervical cancer previously treated with platinum-based chemotherapy.