Adjuvant Chemoradiation and Immunotherapy for Patients With High-Risk Resectable Extrahepatic Cholangiocarcinoma and Gallbladder Cancer: The ACCORD Trial

Extrahepatic cholangiocarcinoma (eCCA) and gallbladder cancer (GBC), which constitute the majority of biliary tract cancers (BTCs), exhibit a significantly elevated risk of recurrence following surgical intervention. Nevertheless, there is a scarcity of adjuvant therapies tailored for patients with resectable eCCA and GBC, and the effectiveness of adjuvant chemotherapy alone is limited. Both immunotherapy and radiotherapy present promising treatment options, with the potential to work synergistically with chemotherapy.

The ACCORD trial, a recent phase 2, multicenter, randomized, controlled trial, enrolled 93 patients with resectable eCCA or GBC after curative resection, randomizing them 1:1 into either a chemoradiation-anti—programmed cell death protein 1 (PD-1) group (n=46) or an observation group (n=47). The chemoradiation-anti–PD-1 group received camrelizumab intravenously every 3 weeks, followed by concurrent chemoradiation using capecitabine and radiotherapy, while the observation group received no anticancer treatment unless relapse was detected. The primary endpoint was overall survival (OS) and secondary endpoints included recurrence-free survival (RFS) and safety.

The results showed a significant improvement in both OS and RFS for the chemoradiation-anti–PD-1 group. The 1-year, 2-year, and 3-year OS rates were 95.7%, 71.4%, and 58.2%, respectively, in the chemoradiation-anti–PD-1 group, compared with 80.9%, 52.9%, and 30.5%, respectively, in the observation group, with a hazard ratio (HR) of 0.43 (95% confidence interval [CI], 0.24-0.79; P=.004). Similarly, the 1-year, 2-year, and 3-year RFS rates were 78.3%, 54.0%, and 40.3%, respectively, in the chemoradiation-anti–PD-1 group, versus 55.3%, 27.0%, and 17.2%, respectively, in the observation group, with an HR of 0.46 (95% CI, 0.28-0.76; P=.001). The chemoradiation-anti–PD-1 treatment was well tolerated, with the main grade 3 adverse events being anemia (15.2%), dermatitis radiation (10.9%), and nausea (10.9%). Importantly, 100% of patients in the treatment group completed the entire course of treatment.

These findings suggest that the combination of chemoradiation and immunotherapy has the potential to improve outcomes for patients with resectable eCCA and GBC, which have historically been associated with high rates of recurrence. The study supports the use of this combination therapy as an effective adjuvant treatment for these high-risk patients.

Source:

Kuang M, Shen S, Chen S, et al. 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). Presented at: ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025; San Francisco, CA; Virtual. Abstract 570.