Universität zu Köln

Peinemann, Frank ORCID: 0000-0002-4727-1313, Baradaran, Sarah, Arnolds, Kevin Bernhard and Hoemberg, Marc ORCID: 0000-0002-6928-7973 (2025). Dual checkpoint inhibitor therapy versus dual targeted therapy of untreated metastatic BRAF-mutant melanoma: a systematic review of randomised controlled trials. BMJ Open, 15 (12). pp. 1-10. BMJ Publishing Group. ISSN 2044-6055

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Abstract

[Artikel-Nr.: e108254] Objective: Dual immune checkpoint inhibitor (ICI) therapy might improve the outcome of adult patients with untreated metastatic BRAF-mutant melanoma. We synthesised the evidence of its effect on overall survival (OS) and adverse events. Design: Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Data sources: MEDLINE and the Cochrane Library were searched through 15 May 2025. Eligibility criteria for selecting studies: We included randomised controlled trials (RCTs) assessing the effects of first-line dual ICI therapy compared with first-line dual targeted therapy (TT) on adult patients with metastatic BRAF-mutant melanoma. We considered articles in English or German language. Data extraction and synthesis: Two independent reviewers extracted data and assessed risk of bias. Time-to-event data were pooled using the generic inverse-variance method and expressed as HRs with 95% CIs. Dichotomous data were pooled using the Mantel-Haenszel method and expressed as risk ratios (RRs). Heterogeneity was assessed (Cochran Q statistic) and quantified (I 2 statistic). GRADE assessed the certainty of the evidence. Results: We identified two RCTs (305 participants) with parallel assignment and intention-to-treat analyses. The primary beneficial outcome was overall survival (OS), and OS favoured the first-line ICI group: HR 0.66 (95% CI 0.49 to 0.90) I 2 =0%. In contrast, the primary adverse outcome was treatment-related adverse events of grade 3 or higher (TRAEs), and TRAE favoured the first-line TT group: RR 1.18 (95% CI 1.01 to 1.39) I 2 =0%. The certainty of the evidence was graded as moderate. Conclusions: The evidence base is compatible with a favourable effect of first-line nivolumab plus ipilimumab for adults with untreated metastatic BRAF-mutant melanoma on survival and an unfavourable effect on toxicity when compared with first-line TT. Future RCTs could provide more data on therapy failure and quality of life. PROSPERO registration number: CRD420251006128.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Peinemann, Frank UNSPECIFIED https://orcid.org/0000-0002-4727-1313 UNSPECIFIED Baradaran, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Arnolds, Kevin Bernhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoemberg, Marc UNSPECIFIED https://orcid.org/0000-0002-6928-7973 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-812123
Identification Number:	10.1136/bmjopen-2025-108254
Journal or Publication Title:	BMJ Open
Volume:	15
Number:	12
Page Range:	pp. 1-10
Number of Pages:	10
Date:	17 December 2025
Publisher:	BMJ Publishing Group
ISSN:	2044-6055
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Kinder- und Jugendmedizin > Klinik und Poliklinik für Kinder- und Jugendmedizin
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81212