Proposal of discontinuation criteria of atezolizumab plus bevacizumab after curative conversion therapy for unresectable early-to-intermediate-stage hepatocellular carcinoma: a multicenter proof-of-concept study
Tomoko Aoki, Masatoshi Kudo, Naoshi Nishida, Kazuomi Ueshima, Kaoru Tsuchiya, Toshifumi Tada, Masahiro Morita, Hirokazu Chishina, Masahiro Takita, Satoru Hagiwara, Hiroshi Ida, Yasunori Minami, Hidekatsu Kuroda, Noriaki Nakamura, Atsushi Hiraoka, Tetsu Tomonari, Joji Tani, Atsushi Naganuma, Satoru Kakizaki, Chikara Ogawa, Takeshi Hatanaka, Toru Ishikawa, Kazuhito Kawata, Atsushi Takebe, Ippei Matsumoto, Masaaki Hidaka, Masayuki Kurosaki, Takashi Kumada, Namiki Izumi
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Source: Crossref
Published: Mar 7, 2025
DOI: 10.1007/s00535-025-02233-z
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Abstract Background Achieving complete response (CR) is a desirable goal in early-to-intermediate-stage hepatocellular carcinoma (HCC). While systemic and locoregional therapies show promise, optimal drug discontinuation criteria remain unclear. This study aims to investigate drug-off criteria for atezolizumab plus bevacizumab as a proof-of-concept study. Methods This retrospective multicenter study included child–pugh class A patients with unresectable HCC without extrahepatic spread or macrovascular invasion who received atezolizumab plus bevacizumab as first-line therapy. Modified clinical CR (mCCR) was defined as CR per mRECIST with sustained normal alpha-fetoprotein (AFP) levels (< 10.0 ng/dl). Recurrence-free survival (RFS) and overall survival (OS) were analyzed based on the “drug-off” criteria defined by following: (1) mRECIST CR with locoregional therapies, (2) sustained normalization of AFP/AFP-L3/ des-gamma-carboxy prothrombin (DCP) for 12–24 weeks, and (3) complete tumor vascularity disappearance by contrast-enhanced ultrasonography (CEUS) or pathological curative resection. Results The median follow-up was 16.5 months (95% CI 15.2–17.8). Among 51 patients achieving mCCR, 11 underwent surgery, with pathological CR in three cases. In contrast, viable lesions were observed in 7 of 40 cases assessed using CEUS. All patients meeting the drug-off criteria ( n = 9) showed no recurrence and none of them experienced mortality, while 45.2% (19/42) of those not meeting the criteria experienced recurrence (median RFS: 12.8 months, p = 0.007). The median OS was not reached in dug-off criteria met patients ( n = 9), 37.7 months (95% CI: NA) in non-criteria met patients ( n = 42), and 27.1 months (95% CI 16.7–37.6) in non-mCCR patients ( n = 184) ( p < 0.001). Conclusion In patients with unresectable and TACE-unsuitable early-to-intermediate-stage HCC who met the drug-off criteria, significantly improved RFS and OS were observed compared those who did not meet the criteria. However, further validation studies are required to confirm the utility of the criteria.
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