Factors influencing the development of cutaneous squamous cell carcinoma in patients on BRAF inhibitor therapy - 17/04/15
Abstract |
Background |
BRAF inhibitors (BRAFi) cause paradoxical activation of the MAPK pathway in keratinocytes resulting in cutaneous squamous cell carcinoma (cuSCC).
Objective |
We sought to examine the clinical factors involved in BRAFi-induced cuSCC development.
Methods |
We studied 134 patients with BRAF-mutant metastatic melanoma treated with a BRAFi at Westmead Hospital, Sydney, Australia. Details of cuSCC development and associations with melanoma clinicopathologic features and treatment outcome were examined.
Results |
In all, 32 (24%) patients developed 110 cuSCC after commencing treatment. In all, 61 (55%) cuSCC developed within the first 3 months. Age was the only independent risk factor for cuSCC development. After 3 months of therapy 4% of patients younger than 40 years developed cuSCC compared with 33% who were older than 60 years, and the hazard ratio of developing a cuSCC increased by 1.7 (95% confidence interval 1.3-2.3) per decade (P < .001). BRAFi cuSCC occurred more often in sun-protected areas (42%) compared with sporadic cuSCC (21%) (P < .001). cuSCC was not associated with progression-free survival.
Limitations |
The study was from a single center and patients were also at risk of sporadic cuSCC.
Conclusion |
Most BRAFi-induced cuSCC develop within 3 months of BRAFi therapy. The only independent risk factor is increasing age. cuSCC may present in anatomical locations with low ultraviolet exposure such that thorough dermatologic assessment is required.
Le texte complet de cet article est disponible en PDF.Key words : BRAF inhibitors, cutaneous squamous cell carcinoma, dabrafenib, melanoma, vemurafenib
Abbreviations used : BRAFi, CI, CSD, cuSCC, ICPMR, MAPK, UV
Plan
| Funding sources: None. |
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| Disclosure: Dr Menzies received honoraria and travel support for conference attendance from GlaxoSmithKline and Roche. Dr Long is a consultant advisor to Roche and GlaxoSmithKline, and has received honoraria from GlaxoSmithKline and Roche. Dr Fernandez-Peñas is a consultant advisor for Roche. Drs Anforth, Byth, Carlos, Chou, Sharma, Scolyer, and Kefford have no conflicts of interest to declare. |
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| Reprints not available from the authors. |
Vol 72 - N° 5
P. 809 - mai 2015 Retour au numéro
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