Saowapa S.Polpichai N.Danpanichkul P.Bernal R.B.Siladech P.Tijani L.Ng K.Wong Y.J.Choudhury A.Saokaew S.Liangpunsakul S.Kaewdech A.Mahidol University2025-07-282025-07-282025-11-01Journal of Clinical and Experimental Hepatology Vol.15 No.6 (2025)09736883https://repository.li.mahidol.ac.th/handle/20.500.14594/111410Background/Aims: Sorafenib, lenvatinib, and atezolizumab combined with bevacizumab (Atezo/Bev) are approved first-line treatments for unresectable hepatocellular carcinoma (uHCC). However, direct comparisons among these therapies remain limited. This study aims to compare the efficacy and safety of Atezo/Bev versus tyrosine-kinase inhibitors (TKIs) as first-line therapies for uHCC. Methods: Two independent authors conducted a literature search using electronic databases (Google Scholar, Medline, and PubMed) and manual reference list reviews up to June 2024. We included studies reporting on overall survival (OS), progression free survival (PFS) or safety data comparing Atezo/Bev versus TKI (sorafenib or lenvatinib) in patients with uHCC, irrespective of study design. Data extraction and statistical analysis were performed using RevMan 5.4. Results: We included a total of 12 studies (Ten retrospective cohort studies, one prospective study, one randomized controlled trial) involving 9952 patients (3560 received Atezo/Bev combination therapy and 6392 received TKI). Atezo/Bev significantly improved OS and PFS compared to lenvatinib (HR: 0.79, 95% CI: 0.71–0.89, P = 0.0001 for OS; HR: 0.76, 95% CI: 0.64–0.90, P = 0.002 for PFS). Atezo/Bev also improved OS in viral patients (HR: 0.72, 95% CI: 0.60–0.86, P = 0.0004), while lenvatinib improved OS (HR: 1.36, 95% CI: 1.13–1.65, P = 0.001) and PFS (HR: 1.46, 95% CI: 1.04–2.05, P = 0.03) in nonviral patients. Atezo/Bev had fewer grade ≥3 adverse events than lenvatinib (OR: 0.43, 95% CI: 0.36–0.51, P = 0.03). Atezo/Bev also demonstrated superior OS and PFS compared to sorafenib (HR: 0.68, 95% CI: 0.57–0.81, P < 0.00001 for OS; HR: 0.67, 95% CI: 0.57–0.77, P < 0.00001 for PFS). Conclusions: Atezo/Bev demonstrates better survival outcomes and safety profile compared to TKI. However, for patients with HCC of nonviral etiology, lenvatinib may be a more suitable alternative.MedicineReviewSCOPUS10.1016/j.jceh.2025.1026332-s2.0-10501115368922133453