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. 2022 Sep:6:e2200018.
doi: 10.1200/PO.22.00018.

BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma

Olivier J van Not  1   2 , Willeke A M Blokx  3 , Alfons J M van den Eertwegh  4 , Melissa M de Meza  1   5   6 , John B Haanen  7 , Christian U Blank  7   8 , Maureen J B Aarts  9 , Franchette W P J van den Berkmortel  10 , Jan Willem B de Groot  11 , Geke A P Hospers  12 , Ellen Kapiteijn  13 , Djura Piersma  14 , Rozemarijn S van Rijn  15 , Marion Stevense-den Boer  16 , Astrid A M van der Veldt  17 , Marye J Boers-Sonderen  18 , Anne M L Jansen  3 , Michel W J M Wouters  1   5   6 , Karijn P M Suijkerbuijk  2
Affiliations

BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma

Olivier J van Not et al. JCO Precis Oncol. 2022 Sep.

Abstract

Purpose: Little is known about the effect of specific gene mutations on efficacy of immune checkpoint inhibitors in patients with advanced melanoma.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

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