Meta-analysis shows improved survival with PD-1/PD-L1 inhibitor plus bevacizumab versus sorafenib in advanced HCC

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BMC gastroenterology Published May 5, 2026 Medically reviewed May 8, 2026 Study authors: Zhong Qisheng, Li Haiying, Hu Wenbin, Li Zhongdong, Hu Zhengqing PubMed ↗ DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider PD-1/PD-L1 inhibitor plus bevacizumab for advanced HCC, noting improved survival but higher serious adverse event rates.

This meta-analysis pooled data from four trials to compare the efficacy and safety of PD-1/PD-L1 inhibitor plus bevacizumab against sorafenib in treatment-naive individuals with advanced hepatocellular carcinoma. The primary outcomes assessed were progression-free survival and overall survival, with secondary outcomes including tumor response rates and adverse event profiles.

The authors observed that the combination therapy resulted in significantly improved overall survival and progression-free survival compared to sorafenib. Additionally, objective response rates and disease control rates were notably higher with the immunotherapy and bevacizumab regimen. These findings suggest a meaningful clinical benefit in extending the time before disease progression and extending life for this patient population.

However, the safety profile revealed higher rates of serious treatment-emergent adverse events and treatment-related adverse events with the combination therapy. Specific grade 3-4 adverse events included hypertension, decreased platelet count, and proteinuria. The authors note that while the tolerability is generally acceptable and manageable, these increased risks require careful monitoring. The study does not report specific discontinuation rates or long-term follow-up periods.

Clinicians should interpret these results with caution, recognizing that the increased survival benefit comes at the cost of a higher burden of serious side effects. The generalizability of subgroup analyses beyond the included trials should not be assumed. This evidence supports the use of the combination in selected patients but underscores the need for vigilant management of potential toxicities.

Study Details

Study typeMeta analysis

Sample sizen = 1,744

EvidenceLevel 1

PublishedApr 2026

PMID42050438

View Original Abstract ↓

BACKGROUND: Sorafenib has served as standard treatment for advanced hepatocellular carcinoma (HCC). Recently, several randomized controlled trials (RCTs) have explored the use of programmed cell death protein 1/programmed death-ligand 1 inhibitor plus bevacizumab (PIB) in alternative first-line regimens; however, the magnitude and consistency of their clinical benefits remain to be systematically quantified. We therefore conducted a meta-analysis aimed at evaluating PIB versus sorafenib regarding efficacy and safety among treatment-naïve individuals with advanced HCC. METHODS: Comprehensive search through 6 data sources was performed to identify phase 3 trials assessing PIB versus sorafenib in the target population. The main endpoints for assessing effectiveness included progression-free survival (PFS) and overall survival (OS). Additional outcomes assessed tumor responses, adverse events (AEs), and patient condition at the time of data cutoff. RESULTS: Four phase 3 RCTs (HEPATORCH, IMbrave150, ORIENT-32, and SCT-I10A-C301) encompassing 1,744 patients were included. Compared with sorafenib, PIB significantly improved the OS (HR: 0.65 [0.57, 0.74], P < 0.00001) and PFS (HR: 0.60 [0.53, 0.67], P < 0.00001). Subgroup analyses showed that the treatment benefits of the PIB group in both PFS and OS were consistent across nearly all subgroups. In addition, the combination regimen achieved significantly higher objective response rate (ORR) and disease control rate (DCR) based on RECIST version 1.1 and mRECIST criteria. However, the PIB group also led to higher rates of serious treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs). The top three grade 3-4 TRAEs reported for PIB patients included hypertension (121/1108, 10.92%), platelet count decreased (58/946, 6.13%), and proteinuria (50/1108, 4.51%). CONCLUSIONS: PIB demonstrates superior survival and tumor response benefits over sorafenib as initial treatment in patients with advanced HCC, with an acceptable and manageable safety profile. PROSPERO ID: CRD 420261294641.