Adjuvant Chemoradiation and Immunotherapy for Extrahepatic Cholangiocarcinoma and Gallbladder Cancer: A Randomized Clinical Trial.

Importance: Extrahepatic cholangiocarcinoma (EHC) and gallbladder cancer (GBC), which make up most biliary tract cancers, have distinct molecular and clinical features compared with intrahepatic cholangiocarcinoma. However, effective adjuvant treatments specifically for patients with resectable EHC and GBC are scarce.

Objective: To evaluate the safety and efficacy of immunotherapy combining with chemoradiotherapy.

Design, Setting, And Participants: In the ACCORD randomized clinical trial, from April 2020 to June 2022, patients with EHC and GBC after curative resection were assessed for eligibility. Patients were randomized 1:1 into to the combination camrelizumab plus concurrent capecitabine and radiotherapy group or the observation group. Data were analyzed from June to August 2024.

Interventions: The intervention group received camrelizumab every 3 weeks after surgery. After 2 courses of camrelizumab treatment, patients received capecitabine with concurrent radiotherapy. Patients in the observation group received no anticancer treatment unless relapse was detected.

Main Outcomes And Measures: The primary end point was overall survival (OS) and the secondary end points included recurrence-free survival (RFS) and safety.

Results: Of 93 included patients, 48 (52%) were female, and the median (range) age was 62 (31-70) years. Patients' baseline characteristics were comparable in the 2 groups. With a median (IQR) follow up of 36 (32-39) months, patients in the combination treatment group significantly better OS and RFS. The 1-year, 2-year and 3-year OS rates were 95.7% (95% CI, 83.7-98.9), 71.4% (95% CI, 56.4-82.5), and 58.2% (95% CI, 40.4-72.4), respectively, in the combination treatment group and 80.9% (95% CI, 66.4-89.5), 52.9% (95% CI, 37.7-65.9), and 30.5% (95% CI, 16.5-45.7), respectively, in the observation group (hazard ratio, 0.43; 95% CI, 0.24-0.79; P = .004). The 1-year, 2-year and 3-year RFS rates were 78.3% (95% CI, 63.4-87.7), 54.0% (95% CI, 38.6-67.1), and 40.3% (95% CI, 25.3-54.8), respectively, in the combination treatment group and 55.3% (95% CI, 40.1-68.1), 27.0% (95% CI, 15.2-40.3), and 17.2% (95% CI, 7.7-29.8), respectively, in the observation group (hazard ratio, 0.46; 95% CI, 0.28-0.76; P < .001). In the combination treatment group, only 6 patients (13%) experienced treatment delay for camrelizumab, and all patients completed the chemoradiation treatment, with no treatment-related deaths.

Conclusions And Relevance: In this randomized clinical trial, camrelizumab plus concurrent capecitabine and radiotherapy as an adjuvant therapy demonstrated superior survival outcomes over observation in patients with resectable EHC/GBC with a well-tolerable safety profile. The observed camrelizumab plus concurrent capecitabine and radiotherapy efficacy warrants further study with active treatment (chemotherapy or chemoradiation therapy) as the control group.

Trial Registration: ClinicalTrials.gov Identifier: NCT04333927.