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Journal of the American Academy of Dermatology
Volume 71, n° 6
page 1102 (décembre 2014)
Doi : 10.1016/j.jaad.2014.09.002
accepted : 2 September 2014
Original Articles

Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma
 

Martina Sanlorenzo, MD a, b, , Aditi Choudhry, MD a, Igor Vujic, MD a, c, Christian Posch, MD a, c, Kim Chong, MD a, Katia Johnston, BSc a, Melissa Meier, MD a, Simona Osella-Abate, MSc b, Pietro Quaglino, MD b, Adil Daud, MD a, Alain Algazi, MD a, Klemens Rappersberger, MD c, Susana Ortiz-Urda, MD, PhD a
a University of California–San Francisco, Mt Zion Cancer Research Center, San Francisco, California 
b Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy 
c Department of Dermatology, Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria 

Reprint requests: Martina Sanlorenzo, MD, Department for Dermatology, University of California–San Francisco, Mt Zion Cancer Research Center, 2340 Sutter St, N461, San Francisco, CA 94115.
Abstract
Background

BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) frequently cause cutaneous adverse events.

Objective

We sought to investigate the cutaneous safety profile of BRAFi versus BRAFi and MEKi combination regimens.

Methods

We performed a retrospective cohort study, collecting data from 44 patients with melanoma treated either with BRAFi (vemurafenib or dabrafenib) or BRAFi and MEKi combination regimens (vemurafenib + cobimetinib or dabrafenib + trametinib). Patient characteristics, and the occurrence and severity of cutaneous adverse events, are described.

Results

The development of cutaneous adverse events was significantly less frequent (P  = .012) and occurred after longer treatment time (P  = .025) in patients treated with BRAFi and MEKi combination regimen compared with patients treated with BRAFi monotherapy. Among patients who received both BRAFi and the combination of BRAFi and MEKi at different time points during their treatment course, the development of squamous cell carcinoma or keratoacanthoma was significantly less frequent when they received the combination regimen (P  = .008). Patients receiving vemurafenib developed more cutaneous adverse events (P  = .001) and in particular more photosensitivity (P  = .010) than patients who did not.

Limitations

There were a limited number of patients.

Conclusion

Combination regimen with BRAFi and MEKi shows fewer cutaneous adverse events and longer cutaneous adverse event-free interval compared with BRAFi monotherapy.

The full text of this article is available in PDF format.

Key words : cutaneous adverse event, histology, inflammation, rash, squamous cell carcinoma, therapy

Abbreviations used : AK, bid, BRAFi, CI, FDA, KA, MAPK, MEKi, SCC



 This study was supported by the National Cancer Institute of the National Institutes of Health (NIH) under award number K08CA155035. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors are also grateful to Timothy Dattels; the Melanoma Research Alliance; and the National Center for Advancing Translational Sciences, NIH (through University of California–San Francisco Clinical and Translational Science Institute Grant Number UL1 TR000004) for their generous support.
 Conflicts of interest: None declared.



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