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. 2023 Aug;149(10):7565-7577.
doi: 10.1007/s00432-023-04678-2. Epub 2023 Mar 28.

Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients

Margherita Rimini  1   2 , Mara Persano  3 , Toshifumi Tada  4 , Goki Suda  5 , Shigeo Shimose  6 , Masatoshi Kudo  7 , Jaekyung Cheon  8 , Fabian Finkelmeier  9 , Ho Yeong Lim  10 , José Presa  11 , Francesca Salani  12   13 , Sara Lonardi  14 , Fabio Piscaglia  15 , Takashi Kumada  16 , Naoya Sakamoto  4 , Hideki Iwamoto  5 , Tomoko Aoki  6 , Hong Jae Chon  7 , Vera Himmelsbach  8 , Marta Schirripa  17   18 , Margarida Montes  10 , Caterina Vivaldi  11   12 , Caterina Soldà  14 , Atsushi Hiraoka  19 , Takuya Sho  4 , Takashi Niizeki  5 , Naoshi Nishida  6 , Christoph Steup  8 , Masashi Hirooka  20 , Kazuya Kariyama  21 , Joji Tani  22 , Masanori Atsukawa  23 , Koichi Takaguchi  24 , Ei Itobayashi  25 , Shinya Fukunishi  26 , Kunihiko Tsuji  27 , Toru Ishikawa  28 , Kazuto Tajiri  29 , Hironori Ochi  30 , Satoshi Yasuda  31 , Hidenori Toyoda  31 , Chikara Ogawa  32 , Takashi Nishimura  33 , Takeshi Hatanaka  34 , Satoru Kakizaki  35 , Noritomo Shimada  36 , Kazuhito Kawata  37 , Fujimasa Tada  19 , Hideko Ohama  19 , Kazuhiro Nouso  21 , Asahiro Morishita  22 , Akemi Tsutsui  24 , Takuya Nagano  24 , Norio Itokawa  23 , Tomomi Okubo  23 , Taeang Arai  23 , Michitaka Imai  28 , Hisashi Kosaka  38 , Atsushi Naganuma  39 , Yohei Koizumi  21 , Shinichiro Nakamura  3 , Masaki Kaibori  38 , Hiroko Iijima  32 , Yoichi Hiasa  20 , Valentina Burgio  40 , Mario Scartozzi  3 , Stefano Cascinu  41   40 , Andrea Casadei-Gardini  41   40
Affiliations

Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients

Margherita Rimini et al. J Cancer Res Clin Oncol. 2023 Aug.

Abstract

Introduction: The best first-line treatment for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class B remains unknown. The aim of the present study was to perform a real-world analysis on a large sample of patients with unresectable HCC with CP B treated with atezolizumab plus bevacizumab Vs Lenvatinib.

Methods: The study population included patients affected by advanced (BCLC-C) or intermediate (BCLC-B) HCC patients not suitable for locoregional therapies from both the Western and Eastern world (Italy, Germany, Republic of Korea and Japan), who received atezolizumab plus bevacizumab or Lenvatinib as first-line treatment. All the study population presented a CP class of B. The primary endpoint of the study was the overall survival (OS) of CP B patients treated with Lenvatinib compared to atezolizumab plus bevacizumab. Survival curves were estimated using the product-limit method of Kaplan-Meier. The role of stratification factors was analyzed with log-rank tests. Finally, an interaction test was performed for the main baseline clinical characteristics.

Results: 217 CP B HCC patients were enrolled in the study: 65 (30%) received atezolizumab plus bevacizumab, and 152 (70%) received lenvatinib. The mOS for patients receiving Lenvatinib was 13.8 months (95% CI: 11.6-16.0), compared to 8.2 months (95% CI 6.3-10.2) for patients receiving atezolizumab plus bevacizumab as first-line treatment (atezolizumab plus bevacizumab Vs Lenvatinib: HR 1.9, 95% CI 1.2-3.0, p = 0.0050). No statistically significant differences were highlighted in terms of mPFS. The multivariate analysis confirmed that patients receiving Lenvatinib as first-line treatment have a significantly longer OS compared to patients receiving atezolizumab plus bevacizumab (HR 2.01; 95% CI 1.29-3.25, p = 0.0023). By evaluating the cohort of patients who received atezolizumab plus bevacizumab, we found that Child B patients with ECOG PS 0, or BCLC B stage or ALBI grade 1 were those who had benefited from the treatment thus showing survival outcomes no significantly different compared to those receiving Lenvatinib.

Conclusion: The present study suggests for the first time a major benefit from Lenvatinib compared to atezolizumab plus bevacizumab in a large cohort of patients with CP B class HCC.

Keywords: Advanced HCC; Atezolizumab; Bevacizumab; Real Word.

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Conflict of interest statement

MK has received Lecture Fee from Bayer, Eisai, MSD, EA Pharma, Chugai; received Research Grant from Chugai, Otsuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Eisai, Bayer, AbbVie, Medico’s Hirata, Astellas Pharma, Bristol-Myers Squibb; received Advisory Consulting fee from MSD, BMS, Taiho, Eisai, Ono pharmaceutical, Chugai. F. F. has received travel support from Ipsen, and speaker’s fees from AbbVie, MSD, Ipsen, Esai and Fresenius. K. M.S. has received grants and personal fees from MERCK, MSD, Servier, EISAI, Amgen. A.C.G. has received grants and personal fees from MSD, Eisai, Bayer, and is an advisor for MSD, Eisai, Bayer, Bristol-Myers Squibb, AstraZeneca and GSK. The other coauthors have no conflict of interest. A.C.G. has received grants and personal fees from MSD, Eisai, Bayer, and is an advisor for MSD, Eisai, Bayer, Bristol-Myers Squibb, AstraZeneca and GSK. The other coauthors have no conflict of interest.

Figures

Fig. 1
Fig. 1
Kaplan Meier for OS (A) and PFS (B) in patients with Child Pugh class B treated with Lenvatinib versus Atezolizumab plus Bevacizumab
Fig. 2
Fig. 2
Kaplan Meier for OS in patients treated with Lenvatinib versus atezolizumab plus bevacizumab according to the ECOG PS (A, B), NLR (C, D), BCLC (E, F), AFP (G, H), ALBI score (I, L)
See this image and copyright information in PMC

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