Predictive factors and survival outcome of conversion therapy for unresectable hepatocellular carcinoma patients receiving atezolizumab and bevacizumab: Comparative analysis of conversion, partial response and complete response patients

Author:

Hatanaka Takeshi1ORCID,Kakizaki Satoru23ORCID,Hiraoka Atsushi4ORCID,Tada Toshifumi5ORCID,Hirooka Masashi6,Kariyama Kazuya7ORCID,Tani Joji8,Atsukawa Masanori9ORCID,Takaguchi Koichi10ORCID,Itobayashi Ei11ORCID,Fukunishi Shinya12,Tsuji Kunihiko13ORCID,Ishikawa Toru14ORCID,Tajiri Kazuto15ORCID,Toyoda Hidenori16ORCID,Ogawa Chikara17,Nishikawa Hiroki18,Nishimura Takashi12ORCID,Kawata Kazuhito19ORCID,Kosaka Hisashi20ORCID,Naganuma Atsushi21ORCID,Yata Yutaka22ORCID,Ohama Hideko23ORCID,Kuroda Hidekatsu24ORCID,Matono Tomomitsu25,Aoki Tomoko26,Kanayama Yuki1,Tanaka Kazunari13,Tada Fujimasa4,Nouso Kazuhiro7ORCID,Morishita Asahiro8ORCID,Tsutsui Akemi10ORCID,Nagano Takuya10,Itokawa Norio9,Okubo Tomomi9,Arai Taeang9,Imai Michitaka14,Nakamura Shinichiro5,Enomoto Hirayuki12,Kaibori Masaki20ORCID,Hiasa Yoichi6ORCID,Kudo Masatoshi26,Kumada Takashi27ORCID,

Affiliation:

1. Department of Gastroenterology Gunma Saiseikai Maebashi Hospital Maebashi Japan

2. Department of Clinical Research NHO 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 Takamatsu 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. Department of Gastroenterology and Hepatology Ogaki Municipal Hospital Ogaki Japan

17. Department of Gastroenterology Japanese Red Cross Takamatsu Hospital Takamatsu Japan

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

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

20. Department of Surgery Kansai Medical University Hirakata Japan

21. Department of Gastroenterology NHO Takasaki General Medical Center Takasaki Japan

22. Department of Gastroenterology Hanwa Memorial Hospital Osaka Japan

23. Department of Gastroenterology Takarazuka City Hospital Takarazuka Japan

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

25. Department of Gastroenterology Hyogo Prefectural Harima‐Himeji General Medical Center Himeji Japan

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

27. Gifu Kyoritsu University Ogaki Japan

Abstract

SummaryAimThis study aims to investigate the predictive factors for conversion therapy in patients with unresectable hepatocellular carcinoma (uHCC) and to evaluate the prognosis of conversion cases by comparing them with partial response (PR) and complete response (CR) cases.MethodsIn this retrospective multicentre study, we included a total of 946 uHCC patients treated with atezolizumab and bevacizumab (Atez/Bev) from September 2020 to September 2023.ResultsOut of the patients, 43 (4.5%) received conversion therapy following Atez/Bev treatment. The overall response rate was 65.1% and 23.7% in the conversion and non‐conversion group, respectively, with a statistical significance (p < 0.001). Multivariate analyses identified that BCLC stage B or an earlier stage (p = 0.045), absence of macrovascular invasion and extrahepatic spread (p = 0.045), and a low value of neutrophil to lymphocyte ratio (p = 0.04) were significantly favourable predictive factors associated with conversion therapy. The conversion group showed significantly better survival compared to the non‐conversion group (p < 0.001). In the landmark analysis at 6, 12 and 18 months, the conversion group exhibited better survival compared to PR patients in the non‐conversion group (p = 0.04, 0.01 and 0.03, respectively) and there were no significant differences in the overall survival (OS) between the conversion group and patients who achieved a CR (p = 0.7, 1.0 and 0.3, respectively).ConclusionsPatients with low tumour burden and low value of NLR were more likely to undergo conversion therapy. The OS of patients undergoing conversion therapy showed better survival compared to those achieving PR and was comparable to those with CR patients. Conversion therapy could be considered if feasible.

Publisher

Wiley

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