Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study

Ji Won Han; Pil Soo Sung; Jae-Sung Yoo; Hee Sun Cho; Soon Kyu Lee; Hyun Yang; Ji Hoon Kim; Heechul Nam; Hae Lim Lee; Hee Yeon Kim; Sung Won Lee; Do Seon Song; Myeong Jun Song; Jung Hyun Kwon; Chang Wook Kim; Si Hyun Bae; Jeong Won Jang; Jong Young Choi; Seung Kew Yoon

doi:10.3389/fonc.2024.1372007

Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study

Front Oncol. 2024 Feb 28:14:1372007. doi: 10.3389/fonc.2024.1372007. eCollection 2024.

Authors

Ji Won Han^{1

2}, Pil Soo Sung^{1

2}, Jae-Sung Yoo^{1

2}, Hee Sun Cho^{1

2}, Soon Kyu Lee^{1

3}, Hyun Yang^{1

4}, Ji Hoon Kim^{1

5}, Heechul Nam^{1

5}, Hae Lim Lee^{1

6}, Hee Yeon Kim^{1

6}, Sung Won Lee^{1

6}, Do Seon Song^{1

7}, Myeong Jun Song^{1

8}, Jung Hyun Kwon^{1

3}, Chang Wook Kim^{1

5}, Si Hyun Bae^{1

4}, Jeong Won Jang^{1

2}, Jong Young Choi^{1

2}, Seung Kew Yoon^{1

2}

Affiliations

¹ The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
² Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
³ Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Republic of Korea.
⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Republic of Korea.
⁶ Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Bucheon, Republic of Korea.
⁷ Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea.
⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.

Abstract

Background: Atezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial.

Materials and methods: This real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177).

Results: First, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups. After PSM, overall survival (OS) was better in the AB group than in the lenvatinib group [hazard ratio (HR)=0.642, P=0.009], but progression-free survival (PFS) did not vary between the two groups (HR=0.817, P=0.132). Objective response rate (ORR) was also similar between AB and lenvatinib (34.8% vs. 30.8%, P=0.581). In a subgroup of patients with objective responses (OR, n=78), OS (HR=0.364, P=0.012) and PFS (HR=0.536, P=0.019) were better in the AB group (n=41) than in the lenvatinib group (n=37). Time-to-progression from time of OR was also better in the AB group (HR=0.465, P=0.012). Importantly, residual liver function was a significant factor related to OS in both treatments. Child-Pugh score following cessation of the respective treatments was better in the AB group (n=105) than in the lenvatinib group (n=126) (median 6 versus 7, P=0.008), and proportion of salvage treatment was also higher in the AB group (52.4% versus 38.9%, P=0.047). When we adjusted for residual liver function or salvage treatment, there was no difference in OS between the two treatments.

Conclusion: Our study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies.

Keywords: HCC; atezolizumab plus bevacizumab; lenvatinib; residual liver function; survival.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022R1I1A1A01063636) (to JH). This work was also supported by the Basic Science Research Program through an NRF grant funded by the Ministry of Science and ICT (grant number: NRF-2019R1A2C3005212) (to PS). This study was supported by Research Fund of Seoul St. Mary's Hospital, The Catholic University of Korea (to JH).