Real-world safety and effectiveness of nivolumab in patients with cancer of unknown primary: results from a nationwide post-marketing surveillance in Japan.

BACKGROUND: Cancer of unknown primary (CUP) is associated with poor prognosis. In December 2021, nivolumab was approved in Japan for the treatment of CUP based on a small phase II trial. This post-marketing surveillance (PMS) evaluated the real-world safety and effectiveness of nivolumab in Japanese patients with CUP. METHODS: This prospective, observational, PMS enrolled patients with CUP who initiated nivolumab between April 2022 and June 2023 at 66 institutions. Patients were observed for 6 months. Safety outcomes were treatment-related adverse events (TRAEs), and effectiveness outcomes included overall response rate (ORR) and overall survival (OS). Analyses were descriptive. RESULTS: Among 151 patients in the safety set, the median age was 70 years and 79.5% had an Eastern Cooperative Oncology Group performance status (PS) 0-1. Any grade and Grade ≥ 3 TRAEs occurred in 25.2% and 11.9% of patients, respectively. Frequently reported TRAEs included interstitial lung disease (3.3%), hepatic function abnormal (2.6%), and hypothyroidism (2.6%). There was one TRAE (neutropenia) resulting in death. In the effectiveness set (n = 144), the ORR was 21.5%. ORR was higher in patients without prior systemic therapy (25.4% vs. 18.2%) and in those with lymph node-only involvement (36.6% vs. 15.5%). The 6-month OS rate was 71.0%, and median OS was not reached. The 6-month OS rates were greater in patients with PS 0-1 and lymph node-only involvement. CONCLUSIONS: Nivolumab was tolerated in patients with CUP in routine practice in Japan, with no new safety concerns, and indicated antitumor activity consistent with clinical trial results. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT2041240121).