Adjuvant chemoradiation combined with immunotherapy for patients with high-risk resectable extrahepatic cholangiocarcinoma and gallbladder cancer: A phase II, multicenter, randomized controlled trial (ACCORD trial).

570 Background: Extrahepatic cholangiocarcinoma (ECC) and gallbladder cancer (GBC), as the majority of biliary tract cancer (BTC), has a markedly high risk of recurrence after surgery. However, adjuvant treatments specifically for resectable ECC and GBC patients are scare and adjuvant chemotherapy alone delivers limited efficacy. Immunotherapy and radiotherapy are potential effective treatments and both of them may synergize with chemotherapy. Methods: ACCORD was a multicenter, phase 2, randomized controlled trial to assess the efficacy and safety of chemoradiation with immunotherapy as an adjuvant treatment in resectable ECC/GBC, compared to observation. The primary endpoint was overall survival (OS) and the secondary endpoints included recurrence-free survival (RFS) and safety. Patients in the chemoradiation-anti-PD-1 group received Camrelizumab intravenously every 3 weeks after surgery. Camrelizumab therapy was not terminated until disease progression, unacceptable toxic effects occurred or informed consent withdrawal. After 2 courses of Camrelizumab treatment, chemoradiation was carried out simultaneously. Patients in the observation group received no anticancer treatment unless relapse was detected. Results: From March 2020 to June 2022, a total of 93 ECC/GBC patients after curative resection were randomized 1:1 into chemoradiation-anti-PD-1 group ( n =46, Camrelizumab + concurrent Capecitabine and radiotherapy) and observation group ( n =47). The 1-year, 2-year and 3-year OS rate were 95.7%, 71.4%, and 58.2% in the chemoradiation-anti-PD-1 group, and 80.9%, 52.9%, 30.5% in the observation group (Hazard ratio (HR) 0.43, 95% confidence interval 0.24-0.79; P =0.004). The 1-year, 2-year and 3-year RFS rate were 78.3%, 54.0%, and 40.3% in the chemoradiation-anti-PD-1 group, and 55.3%, 27.0%, 17.2% in the observation group, with a hazard ratio of 0.46 (95% CI, 0.28 to 0.76; P < 0.001). In the chemoradiation-anti-PD-1 group, the main adverse effect ≥ grade 3 were anemia (7 [15.2%]), dermatitis radiation (5 [10.9%]), and nausea (5 [10.9%]); and 100% of patients completed the whole treatment. Conclusions: Chemoradiation combined with immunotherapy as an adjuvant therapy demonstrated superior survival outcomes over observation in resectable ECC/GBC patients with a well-tolerable safety profile, supporting the potential of this combination treatment as effective adjuvant therapy for these high-risk patients. Clinical trial information: NCT04333927 .