c-Kit inhibitors for unresectable or metastatic mucosal, acral or chronically sun-damaged melanoma: a systematic review and one-arm meta-analysis
Steeb T, Wessely A, Petzold A, Kohl C, Erdmann M, Berking C, Heppt M (2021)
Publication Type: Journal article, Review article
Publication year: 2021
Journal
Book Volume: 157
Pages Range: 348-357
DOI: 10.1016/j.ejca.2021.08.015
Abstract
Background: Activating genomic alterations of the receptor tyrosine kinase KIT are found preferentially in certain melanoma subtypes such as acral and mucosal melanoma or melanoma arising in chronically sun-damaged skin. However, the therapeutic value of c Kit inhibitors for these subtypes currently remains unclear. Objectives: The objective of this study was to summarise the efficacy and safety of c-Kit inhibitors for unresectable or metastatic mucosal, acral or chronically sun-damaged melanoma. Methods: We performed a systematic literature research in MEDLINE, Embase and CENTRAL and hand searched pertinent trial registers and conference abstracts for eligible trials until 23rd June 2020. Results were pooled using a random-effects model to calculate pooled proportions of objective response rates (ORRs) and severe adverse events (sAEs) from unselected KIT mutant or amplified cohorts. Results: Nineteen single-arm studies with an overall sample size of 601 patients were included. The studies investigated imatinib (n = 8), nilotinib (n = 7), dasatinib (n = 3) and sunitinib (n = 1). The pooled ORR for all inhibitors was 15% (95% confidence interval [CI]: 12-18%). Subgroup analysis revealed the highest ORR (20%; 95% CI: 14-26%) for nilotinib. The ORR for mucosal melanoma was 14% (95% CI: 6-24%) and 22% for acral lentiginous melanoma (95% CI: 14-30%). At least one sAE was reported in 42% of patients (95% CI: 34-50%). Conclusions: c-Kit inhibitors represent a valuable treatment option for patients with KIT mutant melanoma, in particular for mutations of exons 11 and 13. Furthermore, high-quality trials are urgently needed to investigate putative combinations of specific targeted therapies with immunotherapy. (c) 2021 Elsevier Ltd. All rights reserved.
Authors with CRIS profile
Anne Petzold
Department of Dermatology
Carola Berking
Lehrstuhl für Haut- und Geschlechtskrankheiten
Markus Heppt
Department of Dermatology
Involved external institutions
Germany (DE)How to cite
APA:
Steeb, T., Wessely, A., Petzold, A., Kohl, C., Erdmann, M., Berking, C., & Heppt, M. (2021). c-Kit inhibitors for unresectable or metastatic mucosal, acral or chronically sun-damaged melanoma: a systematic review and one-arm meta-analysis. European Journal of Cancer, 157, 348-357. https://doi.org/10.1016/j.ejca.2021.08.015
MLA:
Steeb, Theresa, et al. "c-Kit inhibitors for unresectable or metastatic mucosal, acral or chronically sun-damaged melanoma: a systematic review and one-arm meta-analysis." European Journal of Cancer 157 (2021): 348-357.
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