Cutaneous adverse events in patients treated with BRAF inhibitor-based therapies for metastatic melanoma for longer than 52 weeks

Summary Background BRAF inhibitor‐based therapies have been shown to induce cutaneous toxicities, with onset generally in the first 8–26 weeks of therapy. Objectives To determine whether cutaneous toxicities persist in patients who have remained on BRAF inhibitor‐based therapies for longer than 52 w...

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Bibliographic Details
Published in:British journal of dermatology (1951) 2015-01, Vol.172 (1), p.239-243
Main Authors: Anforth, R., Carlos, G., Clements, A., Kefford, R., Fernandez-Peñas, P.
Format: Article
Language:English
Subjects:
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Drug Eruptions - etiology
Female
Humans
Imidazoles - administration & dosage
Imidazoles - adverse effects
Indoles - administration & dosage
Indoles - adverse effects
Male
MAP Kinase Kinase Kinases - antagonists & inhibitors
Melanoma - drug therapy
Middle Aged
Neoplasm Metastasis
Oximes - administration & dosage
Oximes - adverse effects
Prospective Studies
Protein Kinase Inhibitors - administration & dosage
Protein Kinase Inhibitors - adverse effects
Pyridones - administration & dosage
Pyridones - adverse effects
Pyrimidinones - administration & dosage
Pyrimidinones - adverse effects
Skin Neoplasms - drug therapy
Sulfonamides - administration & dosage
Sulfonamides - adverse effects
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Summary:Summary Background BRAF inhibitor‐based therapies have been shown to induce cutaneous toxicities, with onset generally in the first 8–26 weeks of therapy. Objectives To determine whether cutaneous toxicities persist in patients who have remained on BRAF inhibitor‐based therapies for longer than 52 weeks, and therefore whether ongoing dermatology assessment is required. Methods All patients treated with the BRAF inhibitors vemurafenib or dabrafenib or combination BRAF inhibitor and mitogen‐activated protein kinase kinase (MEK) inhibitor therapy at Westmead Hospital, Sydney, Australia underwent regular dermatological assessments for the duration of therapy. All patients enrolled in a clinical trial, and 18% of patients in the compassionate access scheme underwent a baseline assessment prior to commencement of therapy and every 4–8 weeks thereafter. Patients' adverse events were recorded in a specific database. Results Patients continued to develop cutaneous adverse events after 52 weeks of continuous therapy. Patients on single‐agent BRAF inhibitor therapy suffered from Grover disease (45%), plantar hyperkeratosis (45%), verrucal keratosis (18%) and even cutaneous squamous cell carcinoma (16%). The most frequent adverse event seen in patients in the combination BRAF and MEK inhibitor group was an acneiform eruption (40%). Conclusions Patients on BRAF inhibitor‐based therapies need to continue to have regular dermatological follow‐up independent of the duration of their therapy. What's already known about this topic? BRAF inhibitors used in the treatment of mutation‐positive metastatic melanoma induce hyperproliferative cutaneous conditions including cutaneous squamous cell carcinomas. What does this study add? Well‐known BRAF inhibitor‐related cutaneous adverse events are present in patients even after treatment for more than 52 weeks. Cutaneous squamous cell carcinomas continue to develop after 52 weeks of therapy. Patients treated with BRAF inhibitors need to have regular dermatological follow‐up independent of the duration of their therapy.
ISSN:0007-0963
1365-2133
DOI:10.1111/bjd.13200