Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Atezolizumab-bevacizumab (atezo-bev) is recommended as first-line therapy for patients with unresectable hepatocellular carcinoma (uHCC). However, its effectiveness and safety in other populations, including those with Child-Turcotte-Pugh (CTP) class B cirrhosis, is unclear.
Methods: For this systematic review and meta-analysis, electronic databases, including PubMed, Embase, and Scopus, were searched from 1st May, 2020 till 5th October, 2022; the last date of access was January 31, 2023. Pooled progression-free survival (PFS), overall survival (OS), and radiological response rate among patients receiving atezo-bev were compared between patients with CTP-A and CTP-B cirrhosis, with tyrosine kinase inhibitors (TKIs) and among those receiving the drug as first-line and later line therapy. The protocol was registered in Prospero (CRD42022364430).
Findings: Among 47 studies (n = 5400 patients), pooled PFS and OS were 6.86 (95% CI, 6.31-7.41) and 13.8 months (95% CI, 11.81-15.8), respectively. Objective response rate (ORR) and disease control rate were 26.7% (24.6-29.1) and 75.3% (73.1-77.4) using RECIST criteria, and 34% (30.3-37.8) and 73.6% (68.8-78) using mRECIST criteria, respectively. Among those receiving atezo-bev, patients with CTP-B cirrhosis had similar ORRs by RECIST (odds ratio [OR], 1.42 [0.77-2.6]; P = 0.25) and mRECIST criteria (OR, 1.33 [0.52-3.39]; P = 0.53) but shorter PFS (mean difference [MD]:3.83 months [1.81-5.84]) than those with CTP-A cirrhosis. Compared to patients receiving TKIs, those receiving atezo-bev had longer PFS (MD: 2.27 months [0.94-3.5]) and higher ORR (RECIST: OR, 1.44 [1.01-2.04] and mRECIST: OR, 1.33 [1.01-1.75]). Compared to first-line therapy, later-line therapy had lower ORR (RECIST: OR, 1.82 [1.3-2.53]; P < 0.001 and mRECIST: OR, 2.02 [1.34-3.05]) but comparable PFS (MD: 0.58 months [-0.18 to 1.35]) among nine studies. The incidence of grade ≥3 adverse events among patients with CTP-A and CTP-B cirrhosis was comparable (OR, 0.89 [0.45-1.74]) as it was for patients receiving atezo-bev and TKIs (OR, 0.86 [0.61-1.2]).
Interpretation: Our findings suggest that atezo-bev is safe and effective as first-line systemic therapy for patients with uHCC and CTP-A or CTP-B cirrhosis.
Funding: An unsolicited grant from ROCHE Products India Pvt Ltd. was received for publication.
Competing Interests: Dr. Atsushi Hiraoka received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chugai, Lilly, and AstraZeneca. Dr. Takeshi Hatanaka has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Eisai. Dr. Toshifumi Tada has received payment or honoraria for lectures, from Abbvie, Eisai and Chugai. Dr. Ardnt Vogel (AV) has served as a consultant for Roche, Bayer, BMS, EISAI, AstraZeneca, Ipsen, MSD, Sirtex, BTG, Servier, Terumo, Imaging Equipment Ltd (AAA), Böhringer Ingelheim. AV has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Bayer, BMS, EISAI, AstraZeneca, Ipsen, MSD, Sirtex, BTG, Servier, Terumo, Imaging Equipment Ltd (AAA), and Böhringer Ingelheim. AV received support for attending meetings and/or travel from Roche, Bayer, and BMS and participated in the Advisory board for Roche, Bayer, BMS, Lilly, EISAI, AstraZeneca, Ipsen, MSD, Sirtex, BTG, Servier, Terumo, Imaging Equipment Ltd (AAA). Dr. Richard S. Finn has received grants from Roche Genentech, Bayer, BMS, Eisai, Merck, Pfizer, Eli Lilly to institute. RSF is also a consultant for Roche Genentech, AstraZeneca, Bayer, BMS, Eisai, Exelixis CStone Eli Lilly, Pfizer, and Merck and has received support for attending meetings and/or travel from Roche Genentech, Merck, Pfizer, Bayer. RSF has participated for Data Safety Monitoring Board/Advisory Board for AstraZeneca. Dr. Anjana Pillai has served as a consultant for Eisai Inc, Exelixis, Genentech/Roche, AstraZeneca and Replimune. Dr. Amit Singal has served as a consultant for Genentech, AstraZeneca, Eisai, Bayer, Exelixis, Boston Scientific, FujiFilm Medical Sciences, Exact Sciences, Roche, Glycotest, Universal Dx, Freenome, and GRAIL. Other authors have nothing to declare.
(© 2023 The Author(s).)