Long-term vemurafenib therapy in advanced melanoma patients: cutaneous toxicity and prognostic implications

Abstract

Background

The introduction of targeted therapies for the treatment of BRAF-mutated metastatic melanoma was associated with different cutaneous adverse events (AEs).

Objectives

To describe the type, frequency and severity of cutaneous AEs related to vemurafenib; to understand the association between AEs and vemurafenib efficacy in terms of median overall survival (OS) and median progression-free survival (PFS); to identify molecular characteristics of long-term responders.

Methods

This observational, retrospective, monocentric study included all consecutive patients with unresectable stage III or stage IV melanoma and BRAF V600E mutation that started treatment with vemurafenib between May 2012 and May 2014.

Results

62 patients with a median age of 56 years (range 26–82) were enrolled and received vemurafenib for a median period of 7.9 months (range 0.8–63.7). Among them, 45 patients presented at least one skin AE, 12 reduced the dosage due to cutaneous toxicity, and only one firstly reduced and after stopped the therapy. No specific molecular biomarkers were detected in long-term survivors.

Conclusions

Among long-term survivors, skin AEs seem to be less frequent and less severe. Results on multivariable analysis revealed that the presence of at least one G2 toxicity is a protective factor considering PFS, but not in terms of OS.

Keywords:

• Melanoma
• melanoma, cutaneous malignant
• skin neoplasms
• proto-oncogene proteins B-raf
• vemurafenib
• drug-related side effects and adverse reactions
• long term adverse effects
• long-term care
• cancer survivors
• survivors

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Ethics approval

Ethics approval was given by the Ethics Committee of the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) (protocol code IRST172.05/C.E. – 30 July 2015).

Informed consent

Written informed consent was obtained from the patients for publication of the images accompanying this manuscript. A copy of this written consent is available for review from the journal’s Editor-in-Chief.

Author contributions

All authors made substantive intellectual contributions to the published study, and each author listed on the manuscript has seen and approved the submission of the manuscript. Honorarium, grant, or other form of payment was not given to anyone of the authors to produce the manuscript.

Disclosure statement

The authors declare that they have no competing interests.

Data availability statement

The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.