BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma
| Autor: | Olivier J. van Not, Willeke A.M. Blokx, Alfons J.M. van den Eertwegh, Melissa M. de Meza, John B. Haanen, Christian U. Blank, Maureen J.B. Aarts, Franchette W.P.J. van den Berkmortel, Jan Willem B. de Groot, Geke A.P. Hospers, Ellen Kapiteijn, Djura Piersma, Rozemarijn S. van Rijn, Marion Stevense-den Boer, Astrid A.M. van der Veldt, Marye J. Boers-Sonderen, Anne M.L. Jansen, Michel W.J.M. Wouters, Karijn P.M. Suijkerbuijk |
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| Přispěvatelé: | Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Medical Oncology, Radiology & Nuclear Medicine |
| Rok vydání: | 2022 |
| Předmět: |
Cohort Studies
Nivolumab/therapeutic use Cancer Research Oncology Mutation Proto-Oncogene Proteins B-raf/genetics Humans Melanoma/drug therapy Immune Checkpoint Inhibitors/pharmacology Membrane Proteins/genetics GTP Phosphohydrolases/genetics Ipilimumab/therapeutic use Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] |
| Zdroj: | JCO Precision Oncology, 6:e2200018. American Society of Clinical Oncology JCO Precision Oncology, 6 JCO Precision Oncology, 6:e2200018. AMER SOC CLINICAL ONCOLOGY |
| ISSN: | 2473-4284 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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