Perioperative Treatment of High-risk Resectable Cholangiocarcinoma with Hepatic Arterial Infusion Chemotherapy (HAIC) Combined with Atezo/bevacizumab: a Multicenter Phase II Study (NeoBrave CCA)
Among resectable biliary tract cancers (BTC) patients, surgery has historically been the standard treatment, but even with curative surgery, the cure rates remain relatively low, with most patients relapsing in the short term and a 5-year survival rate of approximately 50% or lower. In BTC, numerous exploratory studies on neoadjuvant treatment have been conducted, yielding varying results, but overall indicating that neoadjuvant therapy can enhance R0 resection rates and prolong survival in certain patients, particularly those with borderline resectable and locally advanced BTC. Currently, there remains a lack of large prospective randomized controlled phase III clinical trials confirming the exact benefits of neoadjuvant and adjuvant therapies for BTC. The SWOG 1815 study is a randomized, open-label phase III trial comparing GAP with Gemcitabine/Cisplatin (GC) in patients with advanced BTC. In exploratory subgroup analyses, GAP improved mOS compared to GC in patients with locally advanced disease (19.2 vs. 13.7 months; HR 0.67, 95% CI 0.42-1.06, p = 0.09). Thus, patients with locally advanced disease may benefit more from GAP treatment. In another multi-institutional, single-arm, phase II trial, patients received a total of 4 cycles of preoperative GAP (Gemcitabine 800 mg/m2, Cisplatin 25 mg/m2, nab-Paclitaxel 100 mg/m2, administered on days 1 and 8 of a 21-day cycle) before attempting radical surgical resection. The median follow-up time for all patients was 17 months; the disease control rate was 90%. Therefore, the preoperative neoadjuvant therapy of Gemcitabine, Cisplatin, and nab-Paclitaxel for iCCA is feasible and safe, with no adverse effects on perioperative outcomes. More recently, neoadjuvant D + GemCis was confirmed to result in a higher surgical resection rate among patients with locally advanced BTC, and surgical resection was associated with higher survival rates. The investigators previously explored a prospective phase II study and showed promising results of HAIC using oxaliplatin and 5-fluorouracil for perihilar cholangiocarcinoma (pCCA), with an objective response rate (ORR) of 67.6%, a mPFS of 12.2 months, and a mOS of 20.5 months. Another phase II prospective study enrolled 32 untreated BTC patients and used HAIC combined with anti-PD-1 monoclonal antibody and bevacizumab as a first-line treatment regimen, the ORR was 84.3%, and the disease control rate (DCR) was 96.9%, with one-year PFS and OS rates of 53.8% and 80.4%, respectively.
⁃ 1\. Age: 18-80 years, regardless of gender; 2. Diagnosis of intrahepatic cholangiocarcinoma or perihilar cholangiocarcinoma confirmed by pathological tissue/cytological diagnosis; 3. Meeting the criteria for surgical resection; 4. Presence of high-risk recurrence factors: iCCA (single mass \>5cm, or multiple lesions, or accompanied by satellite lesions, or accompanied by portal vein/hepatic vein invasion, or CA199 \>200U/ml); pCCA (invasion of secondary branches of the bile duct, or invasion of portal vein/hepatic artery, or accompanied by intrahepatic metastasis); 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1; 6. Child-Pugh class A; 7. Normal major organ function, meeting the following standards:
• Blood routine examination:
• A. Hb≥90 g/L; B. ANC≥1.5×10\^9/L; C. PLT≥75×10\^9/L;
• Biochemical examination:
⁃ A. ALB ≥30g/L; B. ALT and AST\<5×ULN; C. TBiL ≤2×ULN; D. Creatinine ≤1.5×ULN; (3) Coagulation function: A. International normalized ratio (INR) ≤1.5×ULN; B. Activated partial thromboplastin time (APTT) ≤1.5×ULN. 8. Subjects voluntarily join this study, sign informed consent, have good compliance, and cooperate with follow-up.