A multicenter prospective study to evaluate the efficacy of resection for initially unresectable hepatocellular carcinoma after atezolizumab combined with bevacizumab (the RACB study).

e16193 Background: The IMbrave150 study demonstrated that atezolizumab plus bevacizumab (atezo+bev) is superior to sorafenib in terms of progression-free survival (PFS) and overall survival, establishing it as the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). The RACB study was conducted to evaluate the efficacy of atezo+bev in enabling conversion surgery for initially unresectable HCC. Methods: This prospective, single-arm, multicenter Phase II trial included patients with technically or oncologically unresectable HCC who had no prior systemic chemotherapy and at least one target lesion based on RECIST version 1.1. Patients received atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) every three weeks. If a patient was deemed resectable based on radiological assessment after 4 cycles of atezo+bev, surgery was performed 3 weeks following an additional cycle of atezolizumab monotherapy. The primary endpoint was PFS, while the secondary endpoints included overall response rate (ORR), overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 minutes after atezo+bev therapy. The study is registered with the Japan Registry of Clinical Trials (jRCTs051210148). Results: From March 2022 to March 2024, 55 patients from 17 centers were enrolled in the study. Five patients were excluded from the efficacy evaluation set due to ineligible lesions or other reasons, leaving a total of 50 patients in the efficacy evaluation set. The complete and partial response rates, based on RECIST, were 0% and 13%, respectively. Median time to best response was 6.6 weeks. Median PFS and 6-month PFS rate were 11.6 months and 59.1%, respectively. The overall resection rate was 52.0%, corresponding to 26 cases including R0 in 20 patients (76.9%), R1 in 2 patients (7.7%), and R2 in 4 patients (15.4%). In the safety analysis set, which included 50 patients, adverse events were observed in 34 cases (68%). Among these, there were 19 Grade 3 or higher events, including one case of Grade 4 upper gastrointestinal bleeding, one case of Grade 4 encephalitis, one case of Grade 4 elevation of transaminase, and one unexpected death after a single cycle of atezolizumab plus bevacizumab. Conclusions: The survival outcome of the RACB study, with a 6-month PFS rate of 59.1%, comparable to the expected rate of 60%, demonstrates the feasibility of conversion surgery following atezo+bev treatment for patients with initially unresectable HCC. Clinical trial information: jRCTs051210148 .