Anti-PD-1 plus nab-paclitaxel and bevacizumab for second-line treatment of cancer of unknown primary (Fudan CUP-002): a phase II trial.

Fudan CUP-002 study (ClinicalTrials.gov identifier: NCT04848597), an investigator-initiated prospective trial, was designed to evaluate the efficacy and safety of an anti-PD-1 antibody in combination with nab-paclitaxel and bevacizumab as a second-line treatment for cancer of unknown primary (CUP). Between June 2, 2021, and April 19, 2024, 48 eligible patients were enrolled. At data cutoff (January 10, 2025), the median follow-up was 27.1 months (95% CI, 20.2 to 37.2). The objective response rate (ORR) was 54.2% (26/48; 95% CI, 40.3% to 67.4%), and the disease control rate (DCR) was 95.8% (46/48; 95% CI, 86.0% to 98.9%). The median progression-free survival (PFS) was 13.1 months (95% CI, 8.0 to 19.6), while the median overall survival (OS) was 25.1 months (95% CI, 14.6 to 29.5). Treatment-related adverse events (TRAEs) of any grade occurred in 46 patients (95.8%). The exploratory analysis identified systemic eosinophil counts as a prognostic biomarker for treatment response and survival outcomes in second-line setting for CUP. However, current experimental systems are unable to provide the established cell lines or animal models needed to investigate therapeutic mechanisms for CUP. Our present study demonstrated that an anti-PD-1 antibody plus nab-paclitaxel and bevacizumab was effective and well-tolerated in the second-line treatment for patients with CUP.Trial registration: ClinicalTrials.gov identifier: NCT04848597.