Organ-specific response to atezolizumab + bevacizumab combination therapy for unresectable hepatocellular carcinoma with extrahepatic metastases: a retrospective cohort study.

Background: The combination of atezolizumab plus bevacizumab is a standard first-line therapy for advanced hepatocellular carcinoma (HCC). However, the liver possesses a uniquely immunosuppressive microenvironment that often leads to discordant therapeutic responses between intrahepatic lesions and extrahepatic metastases. Conventional assessments relying on binary Response Evaluation Criteria in Solid Tumors (RECIST) criteria have failed to capture the organ-specific longitudinal dynamics. This exploratory study evaluated the organ-specific antitumor dynamics of atezolizumab plus bevacizumab in patients with advanced HCC presenting with extrahepatic metastases. Methods: We retrospectively analyzed 42 consecutive patients with extrahepatic metastases who received atezolizumab plus bevacizumab for HCC at Kanazawa University Hospital between October 2020 and November 2024. Best overall response (BOR), objective response rate (ORR), and disease control rate (DCR) were evaluated per RECIST version 1.1. Organ-specific response rates (OSRR), depth of response (DpR), duration of response (DoR), and time to progression (TTP) were also evaluated. Results: The BORs (complete response/partial response/stable disease/progressive disease) were 0/13/15/14 patients, respectively, yielding an ORR of 31% and a DCR of 67%. OSRRs were 30% in the liver, 11% in the lung, 50% in lymph nodes, and 57% in peritoneal dissemination, and 0% in bone and adrenal glands. The median DpR was 1% in the liver, 7% in the lung, -28% in lymph nodes, -32% in peritoneal dissemination, 9% in bone (n=2), and 8% in adrenal glands (n=3), with no significant differences among organs (P=0.31). Median DOR and TTP were 16.5 and 9.7 months for the liver, not reached and 5.5 months for the lung, not reached and 21.3 months for lymph nodes, and 15.9 and 19.8 months for peritoneal dissemination, respectively, without significant differences. Although no statistically significant differences were observed across organs in median DpR (P=0.31), DoR (P=0.37), or TTP (P=0.09), these exploratory comparisons were severely underpowered due to the restricted sample size and subgroup fragmentation. Conclusions: Atezolizumab plus bevacizumab combination therapy showed no significant differences in organ-specific efficacy and demonstrated consistent antitumor effects regardless of intrahepatic disease or metastatic site. elicited objective tumor responses across diverse intrahepatic and extrahepatic sites. While the small sample size precludes a definitive conclusion of uniform efficacy, the descriptive trends showing preserved intrahepatic efficacy support the clinical rationale of this regimen in advanced HCC.