Skip to main content
SpringerLink
Log in

Is Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma Superior Even to Lenvatinib? A Matching-Adjusted Indirect Comparison

  • Short Communication
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

Background

Atezolizumab plus bevacizumab showed superior progression-free and overall survival compared to sorafenib in the IMbrave150 trial. It would therefore be useful to compare the efficacy of lenvatinib and that of atezolizumab plus bevacizumab to determine if a benefit of one therapy against the other exists.

Objective

The aim of the present report was to apply a matching-adjusted indirect comparison (MAIC) to individual participant data (IPD) from patients treated with lenvatinib outside of randomized trials, to aggregate results derived from the IMbrave150 trial.

Patients and methods

Data from 455 patients who received lenvatinib as first-line systemic therapy for unresectable HCC represented the present IPD. Data inclusion were adapted to those reported in the IMbrave150 trial.

Results

Overall survival on atezolizumab plus bevacizumab proved to be superior to lenvatinib (log-rank: 0.001) with a hazard ratio of 0.59 (95% confidence interval 0.46–0.75). The number needed to treat ranged between seven in the first 12 months and five at the 15th month.

Conclusions

The present MAIC highlights that the combination of atezolizumab plus bevacizumab is superior to lenvatinib. However, updated data or sub-analyses of the IMbrave150 trial would provide more robust estimates for such a treatment comparison.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–73.

    Article  CAS  Google Scholar 

  2. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–905.

    Article  CAS  Google Scholar 

  3. Briggs A, Daniele B, Dick K, Evans TRJ, Galle PR, Hubner RA, et al. Covariate-adjusted analysis of the phase 3 REFLECT study of lenvatinib versus sorafenib in the treatment of unresectable hepatocellular carcinoma. Br J Cancer. 2020;122(12):1754–9.

    Article  CAS  Google Scholar 

  4. Casadei-Gardini A, Scartozzi M, Tada T, Yoo C, Shimose S, Masi G, et al. Lenvatinib versus Sorafenib in first-line treatment of unresectable hepatocellular carcinoma: an inverse probability of treatment weighting analysis. Liver Int. 2021. https://doi.org/10.1111/liv.14817.

    Article  PubMed  Google Scholar 

  5. Ren Z, Fan J, Xu J, Bai Y, Xu A, Cang S, et al. Sintilimab plus bevacizumabbiosimilar vs sorafenib as first-line treatment for advanced hepatocellular carcinoma (ORIENT-32). Ann Oncol. 2020;31(suppl_6):S1287.

    Article  Google Scholar 

  6. Bi F, Qin S, Gu S, Bai Y, Chen Z, Wang Z, et al. Donafenib versus sorafenib as first-line therapy in advanced hepatocellular carcinoma: An open-label, randomized, multicenter phase II/III trial. J Clin Oncol. 2020;38(15_suppl):4506.

    Article  Google Scholar 

  7. Signorovitch JE, Sikirica V, Erder MH, Xie J, Lu M, Hodgkins PS, et al. Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research. Value Health. 2012;15(6):940–7.

    Article  Google Scholar 

  8. Guyot P, Ades AE, Ouwens MJ, Welton NJ. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2012;12:9.

    Article  Google Scholar 

  9. Shimose S, Kawaguchi T, Tanaka M, Iwamoto H, Miyazaki K, Moriyama E, et al. Lenvatinib prolongs the progression-free survival time of patients with intermediate-stage hepatocellular carcinoma refractory to transarterial chemoembolization: a multicenter cohort study using data mining analysis. Oncol Lett. 2020;20(3):2257–65.

    Article  CAS  Google Scholar 

  10. Kudo M, Ueshima K, Chan S, Minami T, Chishina H, Aoki T, et al. Lenvatinib as an initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and child-pugh a liver function: a proof-of-concept study. Cancers. 2019;11(8):1084.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the input of Shinichiro Nakamura (Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan), Atsushi Hiraoka (Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan), Kojiro Michitaka (Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan), Masanori Atsukawa (Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan), Masashi Hirooka (Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan), Kunihiko Tsuji (Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan), Toru Ishikawa (Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan), Koichi Takaguchi (Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan), Kazuya Kariyama (Department of Gastroenterology, Okayama City Hospital, Okayama, Japan), Ei Itobayashi (Department of Gastroenterology, Asahi General Hospital, Asahi, Japan), Kazuto Tajiri (Department of Gastroenterology, Toyama University Hospital, Toyama, Japan), Noritomo Shimada (Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan), Hiroshi Shibata (Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan), Hironori Ochi (Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan), Satoshi Yasuda (Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan), Hidenori Toyoda (Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan), Shinya Fukunishi (Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan), Hideko Ohama (Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan), Kazuhito Kawata (Hepatology Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan), Kazuhiro Nouso (Department of Gastroenterology, Okayama City Hospital, Okayama, Japan), Akemi Tsutsui (Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan), Takuya Nagano (Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan), Norio Itokawa (Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan), Korenobu Hayama (Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan), Taeang Arai (Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan), Michitaka Imai (Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan), Kouji Joko (Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan), Yohei Koizumi (Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan), Yoichi Hiasa (Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan).

Author information

Authors and Affiliations

  1. Università Vita-Salute, San Raffaele Hospital-IRCCS, via Olgettina 70, 20132, Milano, Italy

    Andrea Casadei-Gardini & Stefano Cascinu

  2. Department of Medical Oncology, San Raffaele Scientific Institute IRCCS, Milan, Italy

    Andrea Casadei-Gardini & Stefano Cascinu

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

    Toshifumi Tada

  4. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, 830-0011, Japan

    Shigeo Shimose & Takashi Niizeki

  5. Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan

    Takashi Kumada

  6. Department of Medical and Surgical Sciences, DIMEC, Alma Mater Studiorum-University of Bologna, Bologna, Italy

    Alessandro Cucchetti

Authors
  1. Andrea Casadei-Gardini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshifumi Tada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shigeo Shimose
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Kumada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Niizeki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stefano Cascinu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alessandro Cucchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Casadei-Gardini.

Ethics declarations

Funding

No external funding was used in the preparation of this article.

Conflict of Interest

Andrea Casadei Gardini. reports receiving consulting fees from AstraZeneca, Bayer, Eisai, MSD, Ipsen, and IQVIA, and lecture fees from Eisai, Ipsen, Merck Serono, and Roche. Changhoon Yoo reports honoraria from BMS, MSD, Bayer, Eisai, Ipsen, AstraZeneca, and Servier; and research grants from Bayer, Ono, AstraZeneca, and Servier. Toshifumi Tada, Shigeo Shimose, Takashi Kumada, Takashi Niizeki, Stefano Cascinu, and Alessandro Cucchetti declare that they have no conflicts of interest that might be relevant to the contents of this article.

Ethical approval and consent to participate

All patients who participated in the study gave informed consent. The National Data Inspectorate and the Regional Committee for Medical Research Ethics approved the study. The study was performed in accordance with the Declaration of Helsinki.

Consent for publication

Not applicable.

Data availability

The dataset used during the current study is available from the corresponding author on reasonable request.

Code availability

Not applicable.

Author contributions

Conception and design: ACG, AC. Development of methodology and acquired data: all authors. Statistical analysis and interpretation of data: ACG, AC. Writing, review, and revision of the paper: all authors. Approved the final version: all authors. Agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Casadei-Gardini, A., Tada, T., Shimose, S. et al. Is Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma Superior Even to Lenvatinib? A Matching-Adjusted Indirect Comparison. Targ Oncol 16, 249–254 (2021). https://doi.org/10.1007/s11523-021-00803-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-021-00803-8

Search

Navigation