Evidence map›Paper›PMID 39684531›Full record

SynthesisInternational journal of molecular sciences2024

Safety and Efficacy Analysis of Targeted and Immune Combination Therapy in Advanced Melanoma-A Systematic Review and Network Meta-Analysis.

Anna Sára Lengyel, Fanni Adél Meznerics, Noémi Ágnes Galajda, Noémi Gede, Tamás Kói, Alzahra Ahmed Mohammed, Petra Nikolett Péter, Alexandra It Lakatos, Máté Krebs, Dezső Csupor and 4 more

Abstract readSystematic ReviewNetwork Meta-Analysis
In one paragraph

Synthesis in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 2 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

5 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Advances in Pathogenesis and Treatment of Skin Cancer.International journal of molecular sciences · 2025
    Article
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

14 authors.

Anna Sára LengyelDepartment of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary.
Fanni Adél MeznericsDepartment of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary.
Noémi Ágnes GalajdaDepartment of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary.
Noémi GedeCentre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary.
Tamás KóiCentre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary.
Alzahra Ahmed MohammedDepartment of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary.ORCID 0009-0001-8719-4412
Petra Nikolett PéterDepartment of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary.
Alexandra It LakatosCentre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary.
Máté KrebsDepartment of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary.ORCID 0009-0004-6394-4276
Dezső CsuporCentre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary.ORCID 0000-0002-4088-3333
András BánvölgyiDepartment of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary.ORCID 0000-0002-7071-1364
Péter HegyiCentre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary.
Péter HollóDepartment of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary.
Lajos V KeményDepartment of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The combinations of BRAF inhibitor-based targeted therapies with immune checkpoint inhibitors currently represent less common therapeutic approaches in advanced melanoma. The aim of this study was to assess the safety and efficacy of currently available melanoma treatments by conducting a systematic review and network meta-analysis. Four databases were systematically searched for randomized clinical studies that included patients with advanced/metastatic melanoma receiving chemotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitor therapy, or combinations thereof. The primary endpoints were treatment-related adverse events (TRAE), serious adverse events (SAE) of grade ≥ 3 adverse events, therapy discontinuation, progression-free survival (PFS), as well as objective response rate (ORR) and complete response rate (CRR). A total of 63 articles were eligible for our systematic review; 59 of them were included in the statistical analysis. A separate subgroup analysis was conducted to evaluate the efficacy outcomes, specifically in BRAF-positive patients. Triple combination therapy or triple therapy (inhibiting BRAF, MEK and PD1/PDL1 axis) showed significantly longer progression-free survival compared to BRAF + MEK combination therapies (HR = 0.76; 95% CI 0.64-0.9), but similar objective and complete response rates in BRAF-mutated melanoma. This safety analysis suggests that triple therapy is not inferior to combined immune checkpoint inhibitors (ICI) and BRAF/MEK therapies in terms of serious adverse events and therapy discontinuation rates. However, monotherapies and BRAF/MEK combinations showed notable advantage over triple therapy in terms of treatment-related adverse events. Combination strategies including BRAF/MEK-targeted therapies with ICI therapies are effective first-line options for advanced, BRAF-mutant melanoma; however, they are associated with more frequent side effects. Therefore, future RCTs are required to evaluate and identify high-risk subpopulations where triple therapy therapies should be considered.

Indexed as

Immune Checkpoint InhibitorsMelanomaProto-Oncogene Proteins B-rafAntineoplastic Combined Chemotherapy ProtocolsHumansImmunotherapyMolecular Targeted TherapyProgression-Free SurvivalProtein Kinase InhibitorsTreatment OutcomeBRAF protein, humanImmune Checkpoint InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins B-rafadvanced melanomaimmune checkpoint inhibitornetwork meta-analysistargeted therapytriple therapy

Identifiers

PMID39684531
PMCPMC11641726

What OpenQuestion holds

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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 OpenQuestion graph.