Fudan CUP-002 Trial Demonstrates Strong Efficacy of Anti-PD-1 Triple Combination in Second-Line Cancer of Unknown Primary Treatment
核心洞察
The Fudan (搜索) CUP (搜索)-002 phase II trial achieved a 54.2% objective response rate with anti-PD-1, nab-paclitaxel, and bevacizumab combination therapy in 48 cancer of unknown primary (搜索) patients.
Patients experienced a median progression-free survival of 13.1 months and overall survival of 25.1 months in the second-line treatment setting.
The triple combination therapy demonstrated a 95.8% disease control rate with manageable safety profile, offering a promising treatment option for this challenging cancer type.
The Fudan (搜索) CUP (搜索)-002 phase II trial has demonstrated promising efficacy for a triple combination therapy in patients with cancer of unknown primary (搜索) (CUP), a challenging malignancy with limited treatment options. The investigator-initiated prospective study evaluated anti-PD-1 antibody combined with nab-paclitaxel and bevacizumab as second-line treatment, achieving notable response rates and survival outcomes.
Trial Design and Patient Population
The study enrolled 48 eligible patients between June 2, 2021, and April 19, 2024, with a median follow-up of 27.1 months (95% CI, 20.2 to 37.2) at the data cutoff of January 10, 2025. The trial was registered under ClinicalTrials.gov identifier NCT04848597 and specifically focused on evaluating the efficacy and safety of the three-drug combination in the second-line treatment setting.
Efficacy Outcomes
The combination therapy demonstrated substantial clinical activity with an objective response rate (ORR) of 54.2% (26/48 patients; 95% CI, 40.3% to 67.4%). The disease control rate (DCR) reached 95.8% (46/48 patients; 95% CI, 86.0% to 98.9%), indicating that nearly all patients experienced some degree of disease stabilization or response.
Survival outcomes showed encouraging results, with a median progression-free survival (PFS) of 13.1 months (95% CI, 8.0 to 19.6) and median overall survival (OS) of 25.1 months (95% CI, 14.6 to 29.5). These survival metrics represent meaningful clinical benefits for patients with CUP (搜索), a cancer type known for its poor prognosis.
Safety Profile
Treatment-related adverse events (TRAEs) of any grade occurred in 46 patients (95.8%), indicating that while side effects were common, the combination was generally well-tolerated. The study concluded that the anti-PD-1 antibody plus nab-paclitaxel and bevacizumab regimen was both effective and manageable in terms of safety profile.
Biomarker Discovery
An exploratory analysis revealed that systemic eosinophil counts could serve as a prognostic biomarker for treatment response and survival outcomes in the second-line setting for CUP (搜索) patients. This finding may help clinicians identify patients most likely to benefit from the combination therapy.
Research Limitations
The researchers noted significant challenges in CUP (搜索) research, stating that "current experimental systems are unable to provide the established cell lines or animal models needed to investigate therapeutic mechanisms for CUP." This limitation underscores the difficulty in studying this rare cancer type and developing targeted therapies.
The study represents an important advancement in CUP (搜索) treatment, providing evidence for a new therapeutic approach that combines immunotherapy with established chemotherapy agents and anti-angiogenic therapy in the second-line setting.