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. 2015 May;72(5):809-15.e1.
doi: 10.1016/j.jaad.2015.01.018. Epub 2015 Mar 3.

Factors influencing the development of cutaneous squamous cell carcinoma in patients on BRAF inhibitor therapy

Rachael Anforth  1 , Alexander Menzies  2 , Karen Byth  3 , Giuliana Carlos  1 , Shaun Chou  4 , Raghwa Sharma  5 , Richard A Scolyer  6 , Richard Kefford  2 , Georgina V Long  2 , Pablo Fernandez-Peñas  7
Affiliations

Factors influencing the development of cutaneous squamous cell carcinoma in patients on BRAF inhibitor therapy

Rachael Anforth et al. J Am Acad Dermatol. 2015 May.

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.

Keywords: BRAF inhibitors; cutaneous squamous cell carcinoma; dabrafenib; melanoma; vemurafenib.

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