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. 2024 Jun 21;13(6):655-668.
doi: 10.1159/000539897. eCollection 2024 Dec.

Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma with Main Trunk and/or Contralateral Portal Vein Invasion in IMbrave150

Richard S Finn  1 , Peter R Galle  2 , Michel Ducreux  3 , Ann-Lii Cheng  4 , Norelle Reilly  5 , Alan Nicholas  5 , Sairy Hernandez  5 , Ning Ma  5 , Philippe Merle  6 , Riad Salem  7 , Daneng Li  8 , Valeriy Breder  9
Affiliations

Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma with Main Trunk and/or Contralateral Portal Vein Invasion in IMbrave150

Richard S Finn et al. Liver Cancer. .

Abstract

Introduction: Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety in patient subpopulations with Vp4 portal vein tumor thrombosis (PVTT) and other high-risk prognostic factors are reported.

Methods: IMbrave150 was a global, randomized (2:1), open-label, phase 3 study in systemic treatment-naive patients with unresectable HCC; OS and PFS were co-primary endpoints. Exploratory analyses compared the efficacy and safety of atezolizumab 1,200 mg plus bevacizumab 15 mg/kg every 3 weeks versus sorafenib 400 mg twice daily in patients (i) with and without Vp4 PVTT alone and (ii) with and without high-risk prognostic factors.

Results: In patients with Vp4 PVTT, median OS was 7.6 months (95% CI: 6.0-13.9) with atezolizumab plus bevacizumab (n = 48) and 5.5 months (95% CI: 3.4-6.7) with sorafenib (n = 25; HR 0.62 [95% CI: 0.34-1.11]; descriptive p = 0.104). Median PFS in the respective arms was 5.4 months (95% CI: 3.6-6.9) and 2.8 months (95% CI: 1.5-5.3; HR 0.62 [95% CI: 0.35-1.09]; descriptive p = 0.094). In patients without Vp4, median OS was 21.1 months (95% CI: 18.0-24.6) with atezolizumab plus bevacizumab (n = 288) and 15.4 months (95% CI: 12.6-18.6) with sorafenib (n = 140; HR 0.67 [95% CI: 0.51-0.88]; descriptive p = 0.003). Median PFS in the respective arms was 7.1 months (95% CI: 6.1-9.6) and 4.7 months (95% CI: 4.2-6.1; HR 0.64 [95% CI: 0.51-0.81]; descriptive p < 0.001). The high-risk versus non-high-risk populations had similar outcome patterns. In the respective treatment arms, grade ≥3 treatment-related adverse events occurred in 43% and 48% of patients with Vp4 and 46% and 47% of patients without Vp4.

Conclusion: Regardless of VP4 PVTT or other high-risk features of unresectable HCC, which have often resulted in exclusion from other front-line trials, patients benefited from atezolizumab and bevacizumab versus sorafenib.

Keywords: High-risk prognostic factors; Immunotherapy; PD-L1 inhibitor; Portal vein tumor thrombosis; Vp4.

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Conflict of interest statement

Richard S. Finn reports receiving consulting fees from AstraZeneca, Bayer, CStone Pharmaceuticals, Eisai, Eli Lilly, Exelixis, F. Hoffmann-La Roche Hengrui, Merck, and Pfizer; research funding to institution from Adaptimmune, Bristol Myers Squibb, Eisai, Eli Lilly, Merck, Pfizer, and F. Hoffmann-La Roche Ltd; and is an Editorial Board Member of Liver Cancer. Peter R. Galle reports receiving consulting fees from Adaptimmune, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd., Guerbet, Ipsen, Merck Sharp and Dohme, and Sirtex Medical; honoraria from Adaptimmune, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd., Guerbet, Ipsen, Merck Sharp and Dohme, and Sirtex Medical; advisory fees from Adaptimmune, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd., Guerbet, Ipsen, Merck Sharp and Dohme, and Sirtex Medical; and research funding to institution from Bayer and F. Hoffmann-La Roche Ltd. Michel Ducreux reports receiving honoraria, consulting fees, or advisory fees to self from Amgen, AstraZeneca, Bayer, Eli Lilly, F. Hoffmann-La Roche Ltd., Ipsen, Merck Serono, Pierre Fabre, and Servier; travel support from Bayer, Eli Lilly, F. Hoffmann-La Roche Ltd., Ipsen, Merck Sharp & Dohme, and Servier; speaker bureau participation for Amgen, Bayer, Eli Lilly, F. Hoffmann-La Roche Ltd., Ipsen, and Merck Serono; and research funding to institution from Bayer and F. Hoffmann-La Roche Ltd. Ann-Lii Cheng reports receiving research funding to institution from F. Hoffmann-La Roche Ltd. Alan Nicholas is an employee and stockholder of Roche/Genentech. Philippe Merle has had a consulting or advisory role for Bayer, Ipsen, Lilly, Eisai, AstraZeneca, Bristol Myers Squibb, and MSD; received institutional research funding from Ipsen; and travel and accommodation expenses from Bayer and Ipsen. Riad Salem is a consultant for Boston Scientific, Eisai, Genentech, Cook, Sirtex and AstraZeneca. Daneng Li has received honoraria and advisory/consultancy fees from AstraZeneca, Ipsen, Eisai, Exelixis, Coherus, Genentech, QED, Merck, Adagene, Delcath, Servier, Sumitomo, Transthera, and TerSera; and received institutional research funding from Brooklyn Immunotherapeutics and AstraZeneca. Valeriy Breder has received advisory/consultancy fees from F. Hoffmann-La Roche, MSD, Eisai, Bristol Myers Squibb, and Ipsen; and travel and accommodation expenses from F. Hoffmann-La Roche, MSD, Eisai, Bristol Myers Squibb, and Bayer. Ning Ma is an employee and stockholder of Roche/Genentech. Sairy Hernandez is an employee and stockholder of Roche/Genentech.

Figures

Fig. 1.
Fig. 1.
Extent of Vp4 PVTT. Vp4 indicates the presence of a tumor thrombus in the main trunk of the portal vein or a portal vein branch contralateral to the primarily involved lobe (or both). PVTT, portal vein tumor thrombosis.
Fig. 2.
Fig. 2.
a, b OS and PFS in patients with and without Vp4 PVTT. The vertical dashed lines represent 12-, 18-, and 24-month landmark analyses. atezo, atezolizumab; bev, bevacizumab; HR, hazard ratio; NE, not estimable; OS, overall survival; PFS, progression-free survival; PVTT, portal vein tumor thrombosis.
See this image and copyright information in PMC

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