Evidence map›Paper›PMID 41694404›Full record

SynthesisFrontiers in immunology2026

Efficacy and safety of first-line immunotherapy and targeted therapy in advanced HCC: a network meta-analysis with subgroup analysis based on HBV and HCV infection.

Qinfei Li, Hong Li, Haowei Ma, Wei Chen

Abstract readNetwork Meta-AnalysisSystematic Review
In one paragraph

Synthesis in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Qinfei LiWisconsin School of Business, University of Wisconsin-Madison, Madison, WI, United States.
Hong LiSchool of Pharmacy, Duquesne University, Pittsburgh, PA, United States.
Haowei MaDepartment of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH, United States.
Wei ChenDepartment of Pharmacy, Emergency General Hospital, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: We conducted an etiology-stratified network meta-analysis of first-line systemic therapies for advanced HCC to compare newer regimens beyond sorafenib-based RCT evidence (HBV, HCV, or non-viral). Methods: Following PRISMA-NMA, we searched PubMed, Embase, Cochrane Library, and Web of Science to 01 June 2025 for first-line RCTs in advanced/unresectable HCC. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints were objective response rate (ORR) and grade ≥3 adverse events (AEs≥3). A Bayesian fixed-effects NMA (gemtc v4.4 with rjags) reported hazard ratios (HRs) or risk ratios (RRs) with 95% credible intervals, calculated SUCRA values for ranking, and assessed network coherence using deviance information criterion differences between consistency and inconsistency models. Protocol registered in PROSPERO (CRD420251074687). Results: Twenty-four RCTs (n=13,572) evaluating 26 first-line regimens formed a connected evidence network. In the overall population, regimens with significant OS advantage over sorafenib included sintilimab plus bevacizumab biosimilar (HR = 0.57, 95% CrI 0.43-0.75), camrelizumab plus rivoceranib (HR = 0.62, 0.48-0.79), and atezolizumab plus bevacizumab (HR = 0.66, 0.51-0.84). For PFS, top-ranked combinations were camrelizumab plus rivoceranib (HR = 0.52, 0.41-0.66), anlotinib plus penpulimab (HR = 0.53, 0.41-0.68), lenvatinib plus pembrolizumab (HR = 0.55, 0.44-0.68), and sintilimab plus bevacizumab biosimilar (HR = 0.56, 0.45-0.69). ORR was highest with lenvatinib plus pembrolizumab (RR = 8.00, 4.98-12.86). Regarding safety, tislelizumab (RR = 0.42, 0.33-0.52) and nivolumab (RR = 0.45, 0.36-0.56) were associated with the lowest incidence of AEs≥3. Etiology-stratified analyses indicated that, in HBV-related HCC, sintilimab plus bevacizumab biosimilar and atezolizumab plus bevacizumab led OS rankings, with PFS favoring cabozantinib plus atezolizumab and atezolizumab plus bevacizumab. In HCV-related HCC, only atezolizumab plus bevacizumab conferred a significant OS benefit (HR = 0.43, 0.25-0.73), while PFS superiority was observed only for cabozantinib plus atezolizumab (HR = 0.73, 0.54-0.99). In non-viral HCC, the STRIDE regimen (single priming dose tremelimumab plus durvalumab) was the only regimen to significantly improve OS (HR = 0.75, 0.59-0.96). Conclusions: For first-line therapy in advanced HCC, ICI-based combinations with anti-VEGF/anti-angiogenic agents generally outperform sorafenib, with discernible etiology-specific optima: HBV-related HCC favors sintilimab plus bevacizumab biosimilar or atezolizumab plus bevacizumab; HCV-related HCC favors atezolizumab plus bevacizumab; and in non-viral disease, STRIDE demonstrates a unique OS advantage. This etiology-stratified evidence framework may guide individualized first-line decision-making, pending confirmation in head-to-head trials. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251074687, CRD420251074687.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, HepatocellularHepatitis BHepatitis CImmunotherapyLiver NeoplasmsHumansImmune Checkpoint InhibitorsMolecular Targeted TherapyRandomized Controlled Trials as TopicTreatment OutcomeImmune Checkpoint Inhibitorsbayesian network meta-analysisfirst-line therapyHBVHCVhepatocellular carcinomaimmune checkpoint inhibitorstargeted therapy

Identifiers

PMID41694404
PMCPMC12894325

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.