Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed‐effects regression model approach

Author:

Hatanaka Takeshi1ORCID,Kakizaki Satoru23ORCID,Hiraoka Atsushi4ORCID,Tada Toshifumi5ORCID,Hirooka Masashi6,Kariyama Kazuya7ORCID,Tani Joji8,Atsukawa Masanori9,Takaguchi Koichi10ORCID,Itobayashi Ei11,Fukunishi Shinya12,Tsuji Kunihiko13,Ishikawa Toru14ORCID,Tajiri Kazuto15ORCID,Ochi Hironori16,Yasuda Satoshi17,Toyoda Hidenori17ORCID,Ogawa Chikara18,Yokohama Keisuke19,Nishikawa Hiroki19,Nishimura Takashi12ORCID,Shimada Noritomo20,Kawata Kazuhito21ORCID,Kosaka Hisashi22ORCID,Naganuma Atsushi23,Yata Yutaka24ORCID,Ohama Hideko25ORCID,Kuroda Hidekatsu26,Tanaka Kazunari13,Tanaka Takaaki4,Tada Fujimasa4,Nouso Kazuhiro7ORCID,Morishita Asahiro8ORCID,Tsutsui Akemi10,Nagano Takuya10,Itokawa Norio9,Okubo Tomomi9,Arai Taeang9,Imai Michitaka14,Koizumi Yohei6,Nakamura Shinichiro5,Kaibori Masaki22ORCID,Iijima Hiroko12,Hiasa Yoichi6ORCID,Kudo Masatoshi27ORCID,Kumada Takashi28ORCID,

Affiliation:

1. Department of Gastroenterology Gunma Saiseikai Maebashi Hospital Maebashi Japan

2. Department of Clinical Research National Hospital Organization Takasaki General Medical Center Takasaki Japan

3. Department of Gastroenterology and Hepatology Gunma University Graduate School of Medicine Maebashi Japan

4. Gastroenterology Center, Ehime Prefectural Central Hospital Matsuyama Japan

5. Department of Internal Medicine, Japanese Red Cross Himeji Hospital Himeji Japan

6. Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine Matsuyama Japan

7. Department of Gastroenterology, Okayama City Hospital Okayama Japan

8. Department of Gastroenterology and Neurology Kagawa University Kita‐gun Japan

9. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School Tokyo Japan

10. Department of Hepatology, Kagawa Prefectural Central Hospital Takamatsu Japan

11. Department of Gastroenterology, Asahi General Hospital Asahi Japan

12. Department of Gastroenterology, Division of Hepatobiliary and Pancreatic Diseases Hyogo Medical University Nishinomiya Japan

13. Center of Gastroenterology, Teine Keijinkai Hospital Sapporo Japan

14. Department of Gastroenterology, Saiseikai Niigata Hospital Niigata Japan

15. Department of Gastroenterology Toyama University Hospital Toyama Japan

16. Center for Liver‐Biliary‐Pancreatic Disease, Matsuyama Red Cross Hospital Matsuyama Japan

17. Department of Gastroenterology and Hepatology Ogaki Municipal Hospital Japan

18. Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital Takamatsu Japan

19. Department of Gastroenterology Osaka Medical and Pharmaceutical University Osaka Japan

20. Division of Gastroenterology and Hepatology, Otakanomori Hospital Kashiwa Japan

21. Hepatology Division, Department of Internal Medicine II Hamamatsu University School of Medicine Hamamatsu Japan

22. Department of Surgery Kansai Medical University Hirakata Japan

23. Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center Takasaki Japan

24. Department of Gastroenterology, Hanwa Memorial Hospital Osaka Japan

25. Department of Gastroenterology, Takarazuka City Hospital Takarazuka Japan

26. Division of Gastroenterology and Hepatology, Department of Internal Medicine Iwate Medical University Iwate Japan

27. Department of Gastroenterology and Hepatology Kindai University Faculty of Medicine Osaka Japan

28. Department of Nursing Gifu Kyoritsu University Ogaki Japan

Abstract

AbstractAimThis retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma.MethodsWe included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity‐score‐matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed‐effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow‐up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups.ResultsFollowing propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were −2.41 ± 0.40 and −2.44 ± 0.42 at baseline, and −2.17 ± 0.56 and −2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p < 0.001), there was no significant difference in the rate of ALBI score deterioration between the groups (p = 0.06). Subgroup analyses showed that LEN‐treated patients with BCLC advanced stage (p = 0.02) and those who initially received the full dose (p < 0.001) had a significantly greater worsening of ALBI score compared to Atez/Bev.ConclusionsUsing a nonlinear mixed‐effects regression approach, which allowed for the inclusion of cases with treatment interruption, we found no significant difference in the trend of liver function deterioration between the Atez/Bev and LEN groups. Caution should be exercised for LEN‐treated patients with BCLC advanced stage or those receiving the full dose of LEN.

Publisher

Wiley

Subject

Cancer Research,Radiology, Nuclear Medicine and imaging,Oncology

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