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

Anand V Kulkarni; Harshvardhan Tevethia; Karan Kumar; Madhumita Premkumar; Mark D Muttaiah; Atsushi Hiraoka; Takeshi Hatanaka; Toshifumi Tada; Takashi Kumada; Satoru Kakizaki; Arndt Vogel; Richard S Finn; Padaki Nagaraja Rao; Anjana Pillai; Duvvur Nageshwar Reddy; Amit G Singal

doi:10.1016/j.eclinm.2023.102179

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

EClinicalMedicine. 2023 Aug 30:63:102179. doi: 10.1016/j.eclinm.2023.102179. eCollection 2023 Sep.

Authors

Anand V Kulkarni¹, Harshvardhan Tevethia², Karan Kumar³, Madhumita Premkumar⁴, Mark D Muttaiah⁵, Atsushi Hiraoka⁶, Takeshi Hatanaka⁷, Toshifumi Tada⁸, Takashi Kumada⁹, Satoru Kakizaki¹⁰, Arndt Vogel¹¹, Richard S Finn¹², Padaki Nagaraja Rao¹, Anjana Pillai¹³, Duvvur Nageshwar Reddy¹, Amit G Singal¹⁴

Affiliations

¹ Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India.
² Department of Hepatology, ILBS, New Delhi, India.
³ Department of Hepatology, Mahatma Gandhi Medical College, Jaipur, India.
⁴ Department of Hepatology, PGIMER, Chandigarh, India.
⁵ Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁶ Gastroenterology Centre, Ehime Prefectural Central Hospital, Matsuyama, Japan.
⁷ Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.
⁸ Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan.
⁹ Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.
¹⁰ Department of Clinical Research, National Hospital Organization Takasaki General Medical Centre, Takasaki, Japan.
¹¹ Medizinische Hochschule Hannover, Hannover 30625, Germany.
¹² Division of Hematology/Oncology, Department of Medicine, Geffen School of Medicine at UCLA, Santa Monica, CA, USA.
¹³ Division of Gastroenterology, Hepatology and Nutrition, Chicago, IL, USA.
¹⁴ Department of Medicine, UT Southwestern Medical Centre, Dallas, TX, USA.

Abstract

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.

Keywords: Adverse events; Immunotherapy; Liver cancer; Radiological response.