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. 2024 Aug 20;14(2):127-141.
doi: 10.1159/000540969. eCollection 2025 Apr.

Real-World Study of Systemic Treatment after First-Line Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma in Asia-Pacific Countries

Choong-Kun Lee  1   2 , Changhoon Yoo  3 , Jung Yong Hong  4 , Se Jun Park  5 , Jin Won Kim  6 , David Wai Meng Tai  7 , Hyeyeong Kim  8 , Krittiya Korphaisarn  9 , Suebpong Tanasanvimon  10 , San-Chi Chen  11 , Ju Won Kim  12 , Ilhwan Kim  13 , Moonho Kim  14 , Joan Choo  15 , Sang-Bo Oh  16 , Ching-Tso Chen  17 , Woo Kyun Bae  18 , Hongsik Kim  19 , Seok Jae Huh  20 , Chia-Jui Yen  21 , Sejung Park  2 , Dong Ki Lee  1 , Landon Long Chan  22 , Beodeul Kang  23 , Minsu Kang  6 , Raghav Sundar  15 , Hye Jin Choi  1 , Stephen Lam Chan  22 , Hong Jae Chon  23 , Myung-Ah Lee  5
Affiliations

Real-World Study of Systemic Treatment after First-Line Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma in Asia-Pacific Countries

Choong-Kun Lee et al. Liver Cancer. .

Abstract

Introduction: Atezolizumab plus bevacizumab is a commonly used first-line regimen for advanced hepatocellular carcinoma (HCC) treatment owing to its superior outcomes compared to sorafenib. However, optimal subsequent treatment options for patients with HCC who progressed on first-line atezolizumab plus bevacizumab remain unclear.

Methods: This multinational, multi-institutional, retrospective study included patients with HCC from 22 centers in five Asia-Pacific countries who were treated with first-line atezolizumab plus bevacizumab, which was discontinued for any reason. The endpoints included progression-free survival (PFS) and overall survival (OS) according to patient characteristics and second-line regimens.

Results: Between June 2016 and May 2023, 1,141 patients were treated with first-line atezolizumab plus bevacizumab, of whom 629 (55.1%) received subsequent treatment. Sorafenib and lenvatinib were the most commonly administered second-line regimens (53.9% and 25.6%, respectively). Overall, the median PFS and OS were 2.9 and 8.0 months, respectively. Lenvatinib had longer PFS (4.0 vs. 2.3 months) and OS (8.0 vs. 6.3 months) than sorafenib. Patients treated with tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI) (n = 50, 8.3%) showed PFS and OS of 5.4 and 12.6 months, respectively. Lower tumor burden and lenvatinib or TKI plus ICI use were associated with longer second-line PFS. Preserved liver function was associated with improved OS.

Conclusions: In patients with HCC who progressed on first-line atezolizumab plus bevacizumab, sorafenib and lenvatinib were the most commonly used second-line regimens in Asia-Pacific countries, with lenvatinib resulting in longer OS than sorafenib. The second-line TKI plus ICI combination exhibited promising efficacy, suggesting the potential role of continuing ICIs beyond disease progression.

Keywords: Asia-Pacific; Atezolizumab plus bevacizumab; Hepatocellular carcinoma; Real-world data; Second-line treatment.

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Conflict of interest statement

C.-k.L. received honoraria from AstraZeneca, Servier, Dong-A ST, Boryung Pharmaceuticals, and Roche; consulting fees from Roche and Daiichi Sankyo; and research grants or supports from Ono Pharmaceuticals, Celltrion, Boryung Pharmaceuticals, GC Biopharma, and Lunit Inc. C.Y. received honoraria from Servier, Bayer, AstraZeneca, Merck Sharp & Dohme, Eisai, Celgene, Bristol Myers Squibb, Ipsen, Novartis, Boryung Pharmaceuticals, Mundipharma, and Roche and research grants from Servier, Bayer, AstraZeneca, Ono Pharmaceuticals, Ipsen, Boryung Pharmaceuticals, and Lunit Inc. R.S. is on an advisory board for and receives honoraria for talks from Bristol Myers Squibb; is on an advisory board for and receives fees for travel from Eisai; is on an advisory board for and receives fees for talks and travel from Taiho and DiethelmKellerSiberHegner; is on an advisory board for and receives fees for talks and research funding from Merck Sharp & Dohme; is on an advisory board for Merck, Bayer, Novartis, GlaxoSmithKline, Astellas, Pierre-Fabre, and Tavotek; receives honoraria for talks from Eli Lilly; receives honoraria for talks and travel from Roche, AstraZeneca, and Ipsen; receives research funding and patents from Paxman Coolers; receives research funding from Natera; receives patents from Auristone, outside the submitted work; and has pending patents with Auristone and Paxman. S.L.C. serves as an advisory member for AstraZeneca, MSD, Eisai, BMS, Ipsen, and Hengrui and received research funds from MSD, Eisai, Ipsen, SIRTEX, and Zailab and honoraria from AstraZeneca, Eisai, Roche, Ipsen, and MSD. Hong Jae Chon has a consulting or advisory role at Eisai, Roche, Bayer, ONO, MSD, BMS, Celgene, Sanofi, Servier, AstraZeneca, and GreenCross Cell and has received research grants from Roche, Dong-A ST, and Boryung Pharmaceuticals. The other authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
Subsequent treatment distribution after first-line Ate/Bev for APAC patients with HCC (n = 1,141).
Fig. 2.
Fig. 2.
PFS and OS of patients who received second-line therapy. Kaplan-Meier survival curves with PFS (a) and OS (b) in months stratified by second-line treatment regimens (n = 605). TKI, tyrosine kinase inhibitor; ICI, immune checkpoint inhibitor; CI, confidence interval; PFS, progression-free survival; OS, overall survival.
Fig. 3.
Fig. 3.
Correlation between PFS of Ate/Bev and second-line treatment regimens. a Swimmer’s plot showing the PFS1 and PFS2. b, c Correlation between PFS1 and PFS2 for patients treated with second-line TKIs (lenvatinib, sorafenib, regorafenib, or cabozantinib) (b, n = 526) and TKI plus ICIs (c, n = 50). TKI, tyrosine kinase inhibitor; ICI, immune checkpoint inhibitor; PFS, progression-free survival; PFS1, first-line PFS of atezolizumab plus bevacizumab; PFS2, second-line PFS of each indicated treatment regimen.
Fig. 4.
Fig. 4.
Subgroup analyses for second-line PFS and OS. Forest plot of subgroup analysis of PFS (a) and OS (b) for patients receiving second-line regimens (n = 605) according to baseline demographic and disease characteristics after Ate/Bev Tx initiation. HRs for the patient subgroups were obtained from unstratified analyses using the Cox proportional hazards model. The CIs for the subgroup analyses were not adjusted for multiple comparisons. Ref, reference; ECOG, Eastern Cooperative Oncology Group; AFP, α-fetoprotein; MVI, macrovascular invasion; LN, lymph node; mALBI, modified albumin-bilirubin; TKI + ICI, tyrosine kinase inhibitor plus immune checkpoint inhibitor; PFS, progression-free survival; OS, overall survival; Ate/Bev, atezolizumab plus bevacizumab; Tx, next treatment; HRs, hazard ratios; CIs, confidence intervals.
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