Evidence map›Paper›PMID 38751554›Full record

ArticleLiver cancer2024

Balancing Efficacy and Tolerability of First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis.

Ciro Celsa, Giuseppe Cabibbo, David James Pinato, Gabriele Di Maria, Marco Enea, Marco Vaccaro, Salvatore Battaglia, Giacomo Emanuele Maria Rizzo, Paolo Giuffrida, Carmelo Marco Giacchetto and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Liver cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 3 pooled it
–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

15 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
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  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Investigation into the efficiency and prognostic elements of CT-guided ¹²⁵I particle implantation for liver cancer.Cancer imaging : the official publication of the International Cancer Imaging Society · 2025
    Article
  12. Highlighting recent achievements to advance more effective cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2025
    Article
  13. Article
  14. Article
  15. Systemic Therapies for Hepatocellular Carcinoma in India.Journal of clinical and experimental hepatology
    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

13 authors.

Ciro CelsaDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
Giuseppe CabibboDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
David James PinatoDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
Gabriele Di MariaDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
Marco EneaDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
Marco VaccaroDipartimento di Scienze Economiche, Aziendali e Statistiche, University of Palermo, Palermo, Italy.
Salvatore BattagliaDipartimento di Scienze Economiche, Aziendali e Statistiche, University of Palermo, Palermo, Italy.
Giacomo Emanuele Maria RizzoDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
Paolo GiuffridaDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
Carmelo Marco GiacchettoDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
Gabriele RancatoreDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
Maria Vittoria GrassiniDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
Calogero CammàDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Atezolizumab + bevacizumab represent the current standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, direct comparison with other combination treatments including immune checkpoint inhibitors (ICI) + tyrosine kinase inhibitors (TKIs) are lacking. Objectives: This network meta-analysis (NMA) aims to indirectly compare the efficacy and the safety of first-line systemic therapies for unresectable advanced HCC. Method: A literature search of MEDLINE, Embase, and SCOPUS databases was conducted up to October 31, 2022. Phase 3 randomized controlled trials (RCTs) testing TKIs, including sorafenib and lenvatinib, or ICIs reporting overall survival (OS) and progression-free survival (PFS) were included. Individual survival data were extracted from OS and PFS curves to calculate restricted mean survival time. A Bayesian NMA was performed to compare treatments in terms of efficacy (15- and 30-month OS, 6-month PFS) and safety, represented by grade ≥3 (severe) adverse events (SAEs). The incremental safety-effectiveness ratio as measure of net health benefit was calculated as the difference in SAE probability divided by survival difference between the 2 most effective treatments. Results: Nine RCTs enrolling 6,600 patients were included. Atezolizumab plus bevacizumab showed the highest probability (88%) of achieving the 30-month OS landmark. Lenvatinib showed a probability of 86% of achieving best PFS outcomes. ICI monotherapies ranked as most tolerable. Atezolizumab plus bevacizumab showed the best net health benefit for OS, compared to durvalumab plus tremelimumab. When evaluating the net health benefit for PFS, at a willingness-to-risk threshold of 10% of SAEs for life-month gained, atezolizumab plus bevacizumab was favoured in 78% of cases, while at threshold of 30% of SAEs for life-month gained, lenvatinib was favoured in 76% of cases. Conclusions: Atezolizumab plus bevacizumab is the best treatment in terms of net benefit and therefore it should be recommended as standard of care. Compared to atezolizumab plus bevacizumab, lenvatinib monotherapy had the best net benefit for PFS when physicians and patients are available to accept a higher risk of toxicity.

Indexed as

Anti-vascular endothelial growth factorFirst-line treatmentHepatocellular carcinomaImmunotherapySystemic treatmentTyrosin-kinase inhibitors

Identifiers

PMID38751554
PMCPMC11095611

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.