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|Ref Type||Journal Article|
|Authors||van Not OJ, Blokx WAM, van den Eertwegh AJM, de Meza MM, Haanen JB, Blank CU, Aarts MJB, van den Berkmortel FWPJ, de Groot JWB, Hospers GAP, Kapiteijn E, Piersma D, van Rijn RS, Stevense-den Boer M, van der Veldt AAM, Boers-Sonderen MJ, Jansen AML, Wouters MWJM, Suijkerbuijk KPM|
|Title||BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma.|
|Abstract Text||Little is known about the effect of specific gene mutations on efficacy of immune checkpoint inhibitors in patients with advanced melanoma.All patients with advanced melanoma treated with first-line anti-PD-1 or ipilimumab-nivolumab between 2012 and 2021 in the nationwide Dutch Melanoma Treatment Registry were included in this cohort study. Objective response rate, progression-free survival (PFS), and overall survival (OS) were analyzed according to BRAF and NRAS status. A multivariable Cox model was used to analyze prognostic factors associated with PFS and OS.In total, 1764 patients received anti-PD-1 and 759 received ipilimumab-nivolumab. No significant differences in PFS were found in the anti-PD-1 cohort. In the ipilimumab-nivolumab cohort, median PFS was significantly higher for BRAF-mutant melanoma (9.9 months; 95% CI, 6.8 to 17.2) compared with NRAS-mutant (4.8 months; 95% CI, 3.0 to 7.5) and double wild-type (5.3 months; 95% CI, 3.6 to 7.1). In multivariable analysis, BRAF-mutant melanoma was significantly associated with a lower risk of progression or death in the ipilimumab-nivolumab cohort. Median OS was significantly higher for BRAF-mutant melanoma compared with NRAS-mutant and double wild-type melanoma for both immune checkpoint inhibitor regimens.Ipilimumab-nivolumab-treated patients with BRAF-mutant melanoma display improved PFS and OS compared with patients with NRAS-mutant and double wild-type melanoma. BRAF mutation status is a factor to consider while choosing between mono and dual checkpoint inhibition in advanced melanoma.|
|Molecular Profile||Treatment Approach|
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|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
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|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
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|BRAF V600X||melanoma||predicted - sensitive||Ipilimumab + Nivolumab||Clinical Study - Cohort||Actionable||In a retrospective analysis, melanoma patients harboring BRAF V600 mutations (V600E/K/R/D or V600_K601delinsE) treated with the combination of Yervoy (ipilimumab) and Opdivo (nivolumab) demonstrated significantly improved median progression-free survival (10.1 vs 5.2 months; P=0.0057) and median overall survival (not reached vs 16.9 months; P<0.0001) compared to patients without BRAF V600 mutations (PMID: 36130145).||36130145|