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Not, O.J. van; Blokx, W.A.M.; Eertwegh, A.J.M. van den; Meza, M.M. de; Haanen, J.B.; Blank, C.U.; ... ; Suijkerbuijk, K.P.M. (2022)

BRAF and NRAS mutation status and response to checkpoint inhibition in advanced melanoma

Article / Letter to editor
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,...Show morePURPOSE: 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.Show less
All authors
Not, O.J. van; Blokx, W.A.M.; Eertwegh, A.J.M. van den; Meza, M.M. de; Haanen, J.B.; Blank, C.U.; Aarts, M.J.B.; Berkmortel, F.W.P.J. van den; Groot, J.W.B. de; Hospers, G.A.P.; Kapiteijn, E.; Piersma, D.; Rijn, R.S. van; Stevense-den Boer, M.; Veldt, A.A.M. van der; Boers-Sonderen, M.J.; Jansen, A.M.L.; Wouters, M.W.J.M.; Suijkerbuijk, K.P.M.
Date
2022-06-01
Journal
JCO Precision Oncology
Volume
6
DOI
doi:10.1200/PO.22.00018