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    Journal of the American Academy of Dermatology. 2014 Oct 16. pii: S0190-9622(14)01897-0. doi: 10.1016/j.jaad.2014.09.002. pmc: PMC4254519. mid: NIHMS627049
    Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma.
    Sanlorenzo M1,  Choudhry A2,  Vujic I3,  Posch C4,  Chong K5,  Johnston K6,  Meier M7,  Osella-Abate S8,  Quaglino P9,  Daud A10,  Algazi A11,  Rappersberger K12,  Ortiz-Urda S13
    Author information
    1University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California; Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy. Electronic address: martina.sanlorenzo@hotmail.it.
    2University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
    3University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California; Department of Dermatology, Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
    4University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California; Department of Dermatology, Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
    5University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
    6University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
    7University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
    8Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy.
    9Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy.
    10University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
    11University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
    12Department of Dermatology, Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria.
    13University of California-San Francisco, Mt Zion Cancer Research Center, San Francisco, California.
    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.


    Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

    Publikations ID: 25440439
    Quelle: öffnen
     
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