Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study

Christina L. Boull, Samantha Gardeen, Talal Abdali, Edward Li, Jolee Potts, Nathan Rubin, Valerie M. Carlberg, Deepti Gupta, Raegan Hunt, Minnelly Luu, Sheilagh M. Maguiness, Christopher L. Moertel, Hannah Song, Karina L. Vivar, Carrie Coughlin, Jennifer T. Huang, Irene Lara-Corrales

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. Objective: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. Methods: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. Results: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris–like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. Conclusions: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.

Original languageEnglish (US)
Pages (from-to)1554-1561
Number of pages8
JournalJournal of the American Academy of Dermatology
Volume84
Issue number6
DOIs
StatePublished - Jun 2021

Bibliographical note

Funding Information:
Funding sources: Supported by National Institutes of Health grant P30 CA77598 using the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health award number UL1-TR002494 .

Funding Information:
Funding sources: Supported by National Institutes of Health grant P30 CA77598 using the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health award number UL1-TR002494.Research reported in this publication was supported by National Institutes of Health grant P30 CA77598 using the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health award number UL1-TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This project was a result of collaboration from the Pediatric Dermatology Research Alliance. This project was made possible by the support of our colleagues in pediatric oncology, including the following: Susan N. Chi, MD, assistant professor of pediatrics, Harvard Medical School, Department of Pediatric Oncology, Dana-Farber Cancer Institute; Stewart Goldman, MD, division head, Hematology, Oncology, Neuro-Oncology, and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago; Angela Waanders, MD, MPH, director, Precision Medicine Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago; Karen Gauvain, MD, associate professor, Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St Louis; Ashley Hite Meyer, CPNP, Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St Louis; Sarah E.S. Leary, MD, Division of Pediatric Hematology-Oncology, Seattle Children's Hospital, University of Washington School of Medicine; and Frank Y. Lin, MD and Jack M. Su, MD, Pediatric Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas. We thank the following investigators and industry sponsors for allowing us to include patients in clinical trials: Novartis (clinicaltrials.gov identifier: NCT02124772); Genentech, Dr Sabine Meuller, University of California, San Francisco, and Dr Theodore Nicolaides, New York University Langone Health (clinicaltrials.gov identifier: NCT01748149); and Dr Nathan Robinson, Children's Hospital of Los Angeles (clinicaltrials.gov identifier: NCT02285439).

Funding Information:
This project was made possible by the support of our colleagues in pediatric oncology, including the following: Susan N. Chi, MD, assistant professor of pediatrics, Harvard Medical School, Department of Pediatric Oncology, Dana-Farber Cancer Institute; Stewart Goldman, MD, division head, Hematology, Oncology, Neuro-Oncology, and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago; Angela Waanders, MD, MPH, director, Precision Medicine Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago; Karen Gauvain, MD, associate professor, Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St Louis; Ashley Hite Meyer, CPNP, Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St Louis; Sarah E.S. Leary, MD, Division of Pediatric Hematology-Oncology, Seattle Children's Hospital, University of Washington School of Medicine; and Frank Y. Lin, MD and Jack M. Su, MD, Pediatric Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.

Publisher Copyright:
© 2020 American Academy of Dermatology, Inc.

Keywords

  • BRAF inhibitor
  • MEK inhibitor
  • drug reaction
  • medical dermatology
  • oncology
  • pediatric dermatology

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