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BRAF Wild-Type Melanomas During Dabrafenib Treatment for Metastatic BRAF V600E Melanoma

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Key Points

  • Multiple wild-type BRAF melanomas developed within 8 weeks of starting dabrafenib.
  • A new metastasis carried BRAF S467L mutation.

In a case report in JAMA Dermatology, Carrera et al described development of multiple wild-type BRAF melanomas and a metastasis with a different BRAF mutation in a patient receiving dabrafenib (Tafinlar) for BRAF V600E–mutant metastatic melanoma.

Development of Melanomas

As described by the authors, a patient in her 30s developed massive BRAF  V600E melanoma metastasis during her 30th week of pregnancy. After emergency cesarean delivery, oral dabrafenib treatment was started, with partial radiologic response observed within 1 month. Dermatologic digital follow-up aided by confocal microscopy at 8 weeks after the start of dabrafenib revealed four new BRAF wild-type melanomas. Rapid disease progression occurred over the following month, with a new lung and pleura metastasis found to have a BRAF S467L mutation.

The investigators concluded: “Cutaneous malignant tumors are the most frequent adverse events of BRAF inhibitors; therefore, strict dermatologic surveillance in a referral center aided by digital follow-up is mandatory, especially when multiple nevi are present and these drugs are used in an adjuvant setting. In view of our findings, the pathogenesis of the development of new melanomas seems to be different from therapy resistance. Whether paradoxical RAF activation could explain these BRAF wild-type secondary malignant tumors is still unknown.”

Cristina Carrera, MD, PhD, of Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, is the corresponding author of the JAMA Dermatology article.

The authors reported no conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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