LBA39 - Updated efficacy and safety data from IMbrave050: Phase III study of adjuvant atezolizumab (atezo) + bevacizumab (bev) vs active surveillance in patients (pts) with resected or ablated high-risk hepatocellular carcinoma (HCC)

Background

At the pre-specified interim analysis (IA; median follow-up, 17.4 mo), IMbrave050 met its primary endpoint of improved independent review facility (IRF)-assessed recurrence-free survival (RFS) in pts with high-risk HCC. The RFS HR for atezo + bev vs active surveillance was 0.72 (adjusted 95% CI: 0.53, 0.98; P=0.012); overall survival (OS) was immature (HR, 1.42; 95% CI: 0.80, 2.54; Qin Lancet 2023). Here, we report updated analyses.

Methods

IMbrave050 enrolled pts with HCC who had high recurrence risk (based on tumour size and number, vascular invasion and tumour differentiation) following curative-intent resection or ablation. Pts were randomised 1:1 to receive atezo 1200 mg + bev 15 mg/kg IV every 3 weeks (17 cycles) or active surveillance for 1 y; pts were eligible to crossover to atezo + bev following IRF-recurrence. Stratification factors included geographic region and a composite factor comprising the number of high-risk features, curative procedure and use of optional adjuvant transarterial chemoembolisation (1 cycle) post-resection. Secondary endpoints included OS and safety.

Results

The updated RFS HR was 0.90 (95% CI: 0.72, 1.12). At the 2^nd IA, OS remained immature (HR, 1.26; 95% CI: 0.85, 1.87). RFS and OS results were consistent across clinically relevant subgroups. No new safety concerns were observed. Table: LBA39

Clinical cutoff: 3 May 2024. Median follow-up: 35.1 mo.NA, not applicable; NE, not estimable.

Conclusions

In this updated analysis, initial RFS benefit with atezo + bev vs active surveillance was not sustained. OS remained immature but showed numerical improvement from the 1^st IA. The safety profile of atezo + bev remained manageable and consistent with that of each agent and the underlying disease. The benefit–risk profile does not support atezo + bev as an adjuvant therapy for all high-risk HCC. Efficacy follow-up will continue. These results inform future approaches to improve pt outcomes.

Clinical trial identification

NCT04102098.

Editorial acknowledgement

Medical writing assistance was provided by Bena Lim, PhD, of Nucleus Global, an Inizio Company, funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. A. Cheng: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting Fees: Bayer Schering Pharma, BMS, Eisai, Exelixis, Nucleix Ltd, Roche/Genentech, Ipsen, IQVIA, Merck Serono, Novartis, Ono Pharmaceutical, Omega Therapeutics, Inc; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, Eisai, Ipsen, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Abbisko Therapeutics Co., Ltd. A.O. Kaseb: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Bayer, BMS, Eisai, Exelixis, Merch, Roche/Genentech; Financial Interests, Personal, Invited Speaker, Support for attending meetings and/or travel: Roche/Genentech. H.C. Lee: Financial Interests, Personal, Research Grant: AstraZeneca, MSD, Roche. E. Cha: Financial Interests, Personal, Financially compensated role, Employment at Genentech Inc: Genentech Inc. S.P. Hack: Financial Interests, Personal, Stocks or ownership: Roche; Financial Interests, Personal, Full or part-time Employment, Employment at Genentech inc: Genentech Inc.. Q. Lian: Financial Interests, Personal, Stocks or ownership: Roche; Financial Interests, Personal, Full or part-time Employment: Genentech Inc.. J. Spahn: Financial Interests, Personal, Stocks or ownership: Roche; Financial Interests, Personal, Full or part-time Employment: Roche. C. Wu: Financial Interests, Personal, Stocks or ownership: Roche; Financial Interests, Personal, Full or part-time Employment: Roche. P. Chow: Financial Interests, Personal, Research Grant: National Medical Research Council (NMRC), Roche, Sirtex, SingHealth Duke-NUS Programme Grant Award, A*Star, Stratificare, MiRXES, Perspectum, AMiLi, SingHealth Duke-NUS Global Health Institute Pilot Research Grant; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Worrell, IQVIA, AstraZeneca, Omega Therapeutics, BeiGene; Financial Interests, Personal, Other, Honorarium for presentation: Roche, Sirtex, Taiwan Society of Interventional Radiology (TSIR), Philippine Society of Nuclear Medicine, Korean Radioembolization Association, State Key Laboratory of Liver Research (SKLLR), Malaysian Society of Interventional Radiology (MYSIR), Asia-Pacific Primary Liver Cancer Expert Meeting, Malaysian Hepato-pancreato-biliary (MyHPB) Congress, Singapore Hepatology Conference, Hong Kong Liver Cancer and Gastrointestinal Cancer Foundation, Asia-Pacific Association for the Study of the Liver (APASL), JSH International Liver Conference, Bayer Liver Forum, Eastern and Western Association for Liver Tumors (EWALT), Tsinghua Medical Forum, Perspectum (Royal Society ofLondon), Liver Cancer Collaborative Annual Scientific and Clinical Meeting, Korean Radioembolization Association Webinar; Financial Interests, Personal, Other, Travel grant to support attendance at ILCA 2022: Roche Singapore Pte Ltd, Roche Diagnostics Asia Pacific Pte Ltd; Other, Personal, Other, Filling date: 17 August 2020: Cell-based biomarkers of immunotherapy in hepatocellular carcinoma. Pub. No: 10202007868Q;; Financial Interests, Personal, Advisory Board: AUM Biosciences, Perspectum, Sirtex Medical; Financial Interests, Personal, Steering Committee Member: Genentech, Singapore-Samsung Medical Centre (SG-SMC) Joint Lab, IMCB; Financial Interests, Personal, Other, Chief Medical Officer: AVATAMED; Financial Interests, Personal, Stocks or ownership: AVATAMED; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing: Roche, Sirtex. All other authors have declared no conflicts of interest.