Cutaneous Adverse Events to Targeted Therapies and Immuno­therapies in Children: A Retrospective Study of 103 Patients from Two Tertiary Haemato-Oncology Referral Centres

Authors

  • Ayelet Ollech Department of Dermatology, Pediatric Dermatology Service, Sheba Medical Center, Tel-Hashomer, 5262000 Ramat Gan, Israel
  • Michal Yalon
  • Gadi Abebe-Campino
  • Vered Molho-Pessach
  • Eve Finklestein
  • Hodaya Cohen
  • Aviv Barzilai
  • Shani Caspi
  • Shoshana Greenberger

DOI:

https://doi.org/10.2340/00015555-3867

Keywords:

drug cutaneous adverse events, targeted therapies, immunotherapies, paediatrics, oncology

Abstract

Targeted medications and immunotherapies are being developed to specifically target the pathways involved in tumours. There is limited experience with these new medications and their cutaneous side-effects in the paediatric population. A retrospective stu

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References

Hadjadj D, Deshmukh S, Jabado N. Entering the era of precision medicine in pediatric oncology. Nat Med 2020; 26: 1684–1685.

Reyes-Habito CM, Roh EK. Cutaneous reactions to chemotherapeutic drugs and targeted therapy for cancer: part II. targeted therapy. J Am Acad Dermatol 2014; 71: 217e1–e11; quiz 27–8.

Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev 2010; 36: 277–285.

Belum VR, Washington C, Pratilas CA, Sibaud V, Boralevi F, Lacouture ME. Dermatologic adverse events in pediatric patients receiving targeted anticancer therapies: a pooled analysis. Pediatr Blood Cancer 2015; 62: 798–806.

Carlberg VM, Davies OMT, Brandling-Bennett HA, Leary SES, Huang JT, Coughlin CC, Gupta D. Cutaneous reactions to pediatric cancer treatment part II: targeted therapy. Pediatr Dermatol 2021; 38: 18–30.

Boull C, Hook K, Moertel C, Maguiness S. Cutaneous reactions in children treated with the mitogen-activated protein kinase extracellular signal-regulated kinase inhibitor trametinib for neural tumors. Pediatr Dermatol 2017; 34: 90–94.

Song H, Zhong CS, Kieran MW, Chi SN, Wright KD, Huang JT. Cutaneous reactions to targeted therapies in children with CNS tumors: a cross-sectional study. Pediatr Blood Cancer 2019; 66: e27682.

Boull CL, Gardeen S, Abdali T, Li E, Potts, J, Rubin N, et al. Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: a multi-center study. J Am Acad Dermatol 2021; 84: 1554–1561.

Yaeger R, Corcoran RB. Targeting alterations in the RAF-MEK pathway. Cancer Discov 2019; 9: 329–341.

McArthur GA, Chapman PB, Robert C, Larkin J, Haanen JB, Dummer R, et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol 2014; 15: 323–332.

Rizzo D, Ruggiero A, Amato M, Maurizi P, Riccardi R. BRAF and MEK inhibitors in pediatric glioma: new therapeutic strategies, new toxicities. Expert Opin Drug Metab Toxicol 2016; 12: 1397–1405.

Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer 2004; 4: 335–348.

Hammill AM, Wentzel M, Gupta A, Nelson S, Lucky A, Elluru R, et al. Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer 2011; 57: 1018–1024.

Hutt-Cabezas M, Karajannis MA, Zagzag D, Shah S, Horkayne-Szakaly I, Rushing EJ, et al. Activation of mTORC1/mTORC2 signaling in pediatric low-grade glioma and pilocytic astrocytoma reveals mTOR as a therapeutic target. Neuro Oncol 2013; 15: 1604–1614.

Bissler JJ, Franz DN, Frost MD, Belousova E, Bebin EM, Sparagana S, et al. The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma. Pediatr Nephrol 2018; 33: 101–109.

Luke JJ, Flaherty KT, Ribas A, Long GV. Targeted agents and immunotherapies: optimizing outcomes in melanoma. Nat Rev Clin Oncol 2017; 14: 463–482.

Chen AP, Setser A, Anadkat MJ, Cotliar J, Olsen EA, Garden BC, Lacouture ME. Grading dermatologic adverse events of cancer treatments: The Common Terminology Criteria for Adverse Events Version 4.0. J Am Acad Dermatol 2012; 67: 1025–1039.

Anforth R, Fernandez-Penas P, Long GV. Cutaneous toxicities of RAF inhibitors. Lancet Oncol 2013; 14: e11–e18.

Anforth RM, Blumetti TC, Kefford RF, Sharma R, Scolyer RA, Kossard S, et al. Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma. Br J Dermatol 2012; 167: 1153–1160.

Lacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, et al. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist 2013; 18: 314–322.

Carlos G, Anforth R, Clements A, Menzies AM, Carlino MS, Chou S, Fernandez-Peñas P. Cutaneous toxic effects of BRAF inhibitors alone and in combination with MEK inhibitors for metastatic melanoma. JAMA Dermatol 2015; 151: 1103–1109.

Sibaud V. Dermatologic reactions to immune checkpoint inhibitors: skin toxicities and immunotherapy. Am J Clin Dermatol 2018; 19: 345–361.

Sanlorenzo M, Vujic I, Daud A, Algazi A, Gubens M, Luna SA, et al. Pembrolizumab cutaneous adverse events and their association with disease progression. JAMA Dermatol 2015; 151: 1206–1212.

Davis KL, Fox E, Merchant MS, Reid JM, Kudgus RA, Liu, X, et al. Nivolumab in children and young adults with relapsed or refractory solid tumors or lymphoma (ADVL1412): a multicentre, open-label, single-arm, phase 1–2 trial. Lancet Oncol 2020; 21: 541–550.

Geoerger B, Kang HJ, Yalon-Oren M, Marshall LV, Vezina C, Pappo A, et al. Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumor or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial. Lancet Oncol 2020; 21: 121–133.

Cacciotti C, Choi J, Alexandrescu S, Zimmerman MA, Cooney TM, Chordas C, et al. Immune checkpoint inhibition for pediatric patients with recurrent/refractory CNS tumors: a single institution experience. J Neurooncol 2020; 149: 113–122.

Additional Files

Published

2021-07-13

How to Cite

Ollech, A., Yalon, M., Abebe-Campino, G., Molho-Pessach, V., Finklestein, E., Cohen, H., Barzilai, A., Caspi, S., & Greenberger, S. (2021). Cutaneous Adverse Events to Targeted Therapies and Immuno­therapies in Children: A Retrospective Study of 103 Patients from Two Tertiary Haemato-Oncology Referral Centres. Acta Dermato-Venereologica, 101(7), adv00501. https://doi.org/10.2340/00015555-3867