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

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...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Lengyel Anna Sára
Meznerics Fanni Adél
Galajda Noémi Ágnes
Gede Noémi
Kói Tamás
Mohammed Alzahra Ahmed
Péter Petra Nikolett
Lakatos Alexandra
Krebs Máté
Csupor Dezső
Bánvölgyi András
Hegyi Péter
Holló Péter
Kemény Lajos Vince
Dokumentumtípus: Cikk
Megjelent: 2024
Sorozat:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 25 No. 23
Tárgyszavak:
doi:10.3390/ijms252312821

mtmt:35629144
Online Access:http://publicatio.bibl.u-szeged.hu/35700
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520 3 |a 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. 
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700 0 1 |a Galajda Noémi Ágnes  |e aut 
700 0 1 |a Gede Noémi  |e aut 
700 0 1 |a Kói Tamás  |e aut 
700 0 1 |a Mohammed Alzahra Ahmed  |e aut 
700 0 1 |a Péter Petra Nikolett  |e aut 
700 0 1 |a Lakatos Alexandra  |e aut 
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700 0 1 |a Csupor Dezső  |e aut 
700 0 1 |a Bánvölgyi András  |e aut 
700 0 1 |a Hegyi Péter  |e aut 
700 0 1 |a Holló Péter  |e aut 
700 0 1 |a Kemény Lajos Vince  |e aut 
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