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

521 Background: The IMbrave150 study showed that atezolizumab plus bevacizumab (atezo+bev) is superior to sorafenib in progression-free survival and overall survival, making it the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). The RACB study was scheduled to evaluate the efficacy of atezo+bev in achieving conversion surgery for initially unresectable HCC. This time, we report the short-term outcomes of the RACB study. Methods: This prospective, single-arm, multicenter Phase II trial evaluates atezo+bev to achieve conversion surgery in patients with technically or oncologically unresectable HCC. Eligible patients had unresectable HCC without prior systemic chemotherapy and at least one target lesion based on RECIST ver1.1. Patients received atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) every three weeks. If resectable on radiological assessment at 12 weeks, atezolizumab monotherapy was given followed by surgery. The primary endpoint was the progression-free survival. The secondary endpoints included the overall response rate, overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 min after atezo+bev therapy. The study is registered with the Japan Registry of Clinical Trials (jRCTs051210148). Results: Between March 2022 and March 2024, 55 patients from 17 centers were enrolled. Four patients were excluded due to ineligible lesions or other reasons. A total of 50 patients were included in the efficacy evaluation set. Macrovascular invasion and extrahepatic metastases were observed in 38 (76.0%) and 6 patients (12.0%), respectively. Two patients (4.0%) had metachronous extrahepatic metastases without intrahepatic tumors. The complete and partial response rates were 0% and 13% based on RECIST, and 2.2% and 26.1% based on mRECIST. The overall resection rate was 48%, corresponding to 24 cases. R0, R1, and R2 resections were performed in 21 (87.5%), 1 (4.2%), and 2 (8.3%) patients, respectively. Complications ≥Grade III according to the Clavien-Dindo classification included 3 bile leakages, 2 infections, 1 anastomotic leakage, and 1 hemoptysis. There were no surgery-related deaths. Of the 51 patients included in the safety analysis set, adverse events occurred in 34 cases (66.7%), with 16 Grade 3 or higher instances with one Grade 4 upper gastrointestinal bleeding, 1 Grade 4 encephalopathy, and 1 unexpected death after 1 cycle of atezo+bev. Conclusions: The RACB study's short-term outcomes demonstrated the feasibility of conversion surgery after atezo+bev in patients with initially unresectable HCC. The response rate of atezo+bev, as measured by mRECIST, was similar to IMbrave150, with a 48% resection rate, though careful monitoring of severe adverse events is essential. Clinical trial information: 051210148.