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Comparative Study
. 2024 Nov 4;8(11):e0562.
doi: 10.1097/HC9.0000000000000562. eCollection 2024 Nov 1.

Atezolizumab/bevacizumab and lenvatinib for hepatocellular carcinoma: A comparative analysis in a European real-world cohort

Tiago de Castro  1 , Sabrina Welland  1 , Leonie Jochheim  2   3 , Cathrine Leyh  2 , Kateryna Shmanko  4 , Fabian Finkelmeier  5 , Petia Jeliazkova  6 , Andre Jefremow  7 , Maria A Gonzalez-Carmona  8 , Arne Kandulski  9 , Daniel Roessler  10 , Najib Ben Khaled  10 , Stefan Enssle  10 , Marino Venerito  11 , Thorben W Fründt  12 , Michael Schultheiß  13   14 , Angela Djanani  15 , Maria Pangerl  16 , Andreas Maieron  17 , Thomas C Wirth  1 , Jens U Marquardt  18 , Richard Greil  19 , Christina Fricke  17 , Rainer Günther  16 , Andreas Schmiderer  15 , Dominik Bettinger  13 , Henning Wege  12 , Bernhard Scheiner  20 , Martina Müller  9 , Christian P Strassburg  8 , Jürgen Siebler  7 , Ursula Ehmer  6 , Oliver Waidmann  5   20 , Arndt Weinmann  4 , Matthias Pinter  21 , Christian M Lange  2   10 , Anna Saborowski  1 , Arndt Vogel  1
Affiliations
Comparative Study

Atezolizumab/bevacizumab and lenvatinib for hepatocellular carcinoma: A comparative analysis in a European real-world cohort

Tiago de Castro et al. Hepatol Commun. .

Abstract

Background: Immunotherapy-based combinations are currently the standard of care in the systemic treatment of patients with HCC. Recent studies have reported unexpectedly long survival with lenvatinib (LEN), supporting its use in first-line treatment for HCC. This study aims to compare the real-world effectiveness of LEN to atezolizumab/bevacizumab (AZ/BV).

Methods: A retrospective analysis was conducted to evaluate the effectiveness and safety of frontline AZ/BV or LEN therapy in patients with advanced HCC across 18 university hospitals in Europe.

Results: The study included 412 patients (AZ/BV: n=207; LEN: n=205). Baseline characteristics were comparable between the 2 treatment groups. However, patients treated with AZ/BV had a significantly longer median progression-free survival compared to those receiving LEN. The risk of hepatic decompensation was significantly higher in patients with impaired baseline liver function (albumin-bilirubin [ALBI] grade 2) treated with AZ/BV compared to those with preserved liver function. Patients with alcohol-associated liver disease had poorer baseline liver function compared to other etiologies and exhibited a worse outcome under AZ/BV.

Conclusions: In this real-world cohort, survival rates were similar between patients treated with LEN and those treated with AZ/BV, confirming that both are viable first-line options for HCC. The increased risk of hepatic decompensation in patients treated with AZ/BV who have impaired baseline liver function underscores the need for careful monitoring. Future trials should aim to distinguish more clearly between metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease.

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Conflict of interest statement

Tiago de Castro received speaker honoraria from AstraZeneca and BMS, and travel support from MSD. Sabrina Welland received speaker honoraria from AstraZeneca. Leonie Jochheim received speaker honoraria from Falk Foundation, Boston scientific, Abbvie, AstraZeneca, and travel support from Biotest and Abbvie; she is consultant for Boston scientific and AstraZeneca. Fabian Finkelmeier received speaker honoraria from AbbVie, MSD, Ipsen, Astra, and travel support from Ipsen, Abbvie, AstraZeneca. Maria A. Gonzalez-Carmona received advisory honoraria from BMS, AZ, Lilly, Roche, MSD, Eisai, Amgen and travel support from AstraZeneca, Lilly, and BMS. Arne Kandulski received advisory honoraria and travel support from Roche, Eisai, Abbvie, Janssen-Cilag, MSD, Boston Scientific, Fujifilm, Micro-Tech Germany, and Bayer. Daniel Roessler received advisory honoraria from Bayer and Ipsen; he received grants from Ipsen. Najib Ben Khaled has received reimbursement of meeting attendance fees and travel support from EISAI and lecture honoraria from the Falk Foundation and AstraZeneca. Marino Venerito received speaker, consultancy, and advisory honoraria from Servier, Roche, BMS, MSD, EISAI, Bayer, Lilly, AstraZeneca, Merck Serono, Sirtex, Ipsen, Nordic Pharma, and Amgen. Michael Schultheiß received speaker honoraria from Falk Foundation, W. L. Gore & Associates, Roche, and Bentley InnoMed. He is a consultant for Bayer. Andreas Maieron received speaker honoraria from Eisai, MSD, and Roche and travel support from Roche; he is a consultant for AstraZeneca, Eisai, Ipsen, MSD, and Roche. Jens U. Marquardt received speaker and advisory honoraria from Roche, MSD, and Eisai, and travel support from AstraZeneca and Ipsen. Thomas C. Wirth is a consultant for Ipsen, Roche, Novartis, BMS, MSD, Daiichi Sankyo, Servier, Merck, Astrazeneca, Pierre Fabre, and Viatris and received grants from Hookipa Biotech and BMS. Richard Greil owns stocks or other ownership from Novo Nordisk and Lilly; he also received honoraria from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, Abbvie, Gilead, Daiicho Sankyo, and Sanofi, and research funding from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, Abbvie, Gilead, and Daiichi Sankyo, and travel support from Roche, Amgen, Janssen, AstraZeneca, Novartis, MSD, Celgene, Gilead, BMS, Abbvie, and Daiichi Sankyo, and consulting honoraria from Celgene, Novartis, Roche, BMS, Takeda, Abbvie, AstraZeneca, Janssen, MSD, Amgen, Merck, Gilead, Daiichi Sankyo, and Sanofi. Richard Greil received advisory honoraria from Roche and Eisai. Dominik Bettinger received speaker honoraria from W. L. Gore & Associates and travel support from Gilead. Henning Wege received consulting and speaker honoraria from Roche, AstraZeneca, and Eisai. Bernhard Scheiner received grant support from AstraZeneca and Eisai, speaker honoraria from Eisai and travel support from AbbVie, AstraZeneca, Ipsen, and Gilead. Jürgen Siebler received speaker honoraria from Ipsen, advisory honoraria from BMS, Lilly, and MSD, and travel support from Celgene. Ursula Ehmer received speaker honoraria from AstraZeneca, Falk Foundation, Ipsen, MSD, and Novartis, and travel support from AstraZeneca; she is a consultant for AstraZeneca, Bayer, Eisai, and MSD. Oliver Waidmann is a consultant and received speaker and investigator honoraria from AstraZeneca, Bayer, Eisai, MSD, and Roche. Arndt Weinmann received speaker honoraria from Eisai, Ipsen and MSD; he is a consultant for Bayer, BMS, Sanofi, Roche, AstraZeneca, and Servier. Matthias Pinter received speaker honoraria from Bayer, BMS, Eisai, Lilly, MSD, and Roche and travel support from Bayer, BMS, Ipsen, and Roche; he is a consultant for AstraZeneca, Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche. Christian M. Lange has received advisory and speaker honoraria from AbbVie, AstraZeneca, Boston Scientific, CSL Behring, Eisai, Falk, Gilead, MSD, Norgine, Novartis, Roche, Shionogi, and Sobi. Anna Saborowski is a consultant and received speaker honoraria from Eisai, Roche, Servier, Ipsen, Lilly, AstraZeneca, MSD, and travel support from Ipsen, Servier, Pierre-Fabre, and MSD. Arndt Vogel received personal fees from Roche, Bayer, BMS, Lilly, EISAI, AstraZeneca, Ipsen, MSD, Sirtex, BTG, Servier, Terumo, and Imaging Equipment Ltd (AAA). Cathrine Leyh, Kateryna Shmanko, Petia Jeliazkova, Andre Jefremow, Thorben W. Fründt, Angela Djanani, Maria Pangerl, Christina Fricke, Andreas Schmiderer, Stefan Enssle, Martina Müller, and Christian P. Strassburg have no conflicts to report.

Figures

None
Graphical abstract
FIGURE 1
FIGURE 1
Kaplan-Meier analysis of (A) overall survival and (B) progression-free survival for patients treated with first-line LEN and AZ/BV. Abbreviations: AZ/BV, atezolizumab plus bevacizumab; LEN, lenvatinib; mOS, median overall survival; mPFS, median progression-free survival; No., number.
FIGURE 2
FIGURE 2
Forrest plot of unadjusted HRs for (A) overall survival and (B) progression-free survival in patients treated with first-line LEN and AZ/BV. Abbreviations: AFP, alfa-feto protein; ALBI, albumin-bilirubin grade; ALD, alcohol-associated liver disease; AZ/BV, atezolizumab plus bevacizumab; CPS, Child-Pugh score; ECOG, European Cooperative Oncology Group performance status; EHS, extrahepatic spread; MASLD, metabolic dysfunction–associated steatotic liver disease; n, number of events reached/total of patients; PVI, portal vein invasion.
FIGURE 3
FIGURE 3
Kaplan-Meier analysis of (A, C) overall survival and (B, D) progression-free survival for patients treated with first-line LEN and AZ/BV, stratified by etiology. Abbreviations: ALD, alcohol-associated liver disease; AZ/BV, atezolizumab plus bevacizumab; LEN, lenvatinib; MASLD, metabolic dysfunction–associated steatotic liver disease; mOS, median overall survival; mPFS, median progression-free survival; No., number.
FIGURE 4
FIGURE 4
Mean ALBI score at baseline and EOT and respective change (Δ) according to (A) treatment cohort, (C) ALBI grade, and (D) etiology. The gray area indicates the range of ALBI grade 2 (>−2.60 to ≤−1.39). Kaplan-Meier analysis of overall survival for patients with (B) worsening ALBI score, (E) worsening ascites, and (F) worsening HE at EOT. Abbreviations: ALBI, albumin-bilirubin; ALD, alcohol-associated liver disease; AZ/BV, atezolizumab/bevacizumab; EOT, end of treatment; LEN, lenvatinib; MASLD, metabolic dysfunction–associated steatotic liver disease; mOS, median overall survival; No., number; w/o, without; w/, with; wors., worsening.
FIGURE 5
FIGURE 5
Kaplan-Meier analysis of (A) overall survival in patients receiving 2L and (B) patients receiving best supportive care (BSC) after first-line LEN and AZ/BV. Abbreviations: AZ/BV, atezolizumab/bevacizumab; 2L, second-line systemic therapy; LEN, lenvatinib; mOS, median overall survival; No., number.
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