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Journal of the American Academy of Dermatology
Volume 77, n° 5
page 902 (novembre 2017)
Doi : 10.1016/j.jaad.2017.06.044
accepted : 18 June 2017
Original Articles

Pigmentary changes in patients treated with targeted anticancer agents: A systematic review and meta-analysis
 

Julia Dai, MD a, b, Viswanath R. Belum, MD a, Shenhong Wu, MD, PhD c, d, Vincent Sibaud, MD e, Mario E. Lacouture, MD a,
a Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 
b Department of Dermatology, Stanford University, Stanford, California 
c Division of Medical Oncology, Department of Medicine, State University of New York at Stony Brook, Stony Brook, New York 
d Division of Hematology and Oncology, Department of Medicine, Northport Veterans Administration Medical Center, Northport, New York 
e Department of Dermatology, Institut Claudius Regaud-Institut Universitaire du Cancer, Toulouse Oncopole, France 

Correspondence to: Mario. E. Lacouture, MD, Dermatology Service, Memorial Sloan Kettering Cancer Center, 60th Street Outpatient Center, Suite 407, Room 4312, 16 East 60th St, New York, NY 10022.Dermatology ServiceMemorial Sloan Kettering Cancer Center60th Street Outpatient CenterSuite 407Room 4312, 16 East 60th StNew YorkNY10022
Abstract
Background

The discovery of signaling networks that drive oncogenic processes has led to the development of targeted anticancer agents. The burden of pigmentary adverse events from these drugs is unknown.

Objective

To conduct a systematic review and meta-analysis of published clinical trials and determine the incidence and risk of development of targeted therapy–induced pigmentary changes.

Methods

A comprehensive search was conducted to identify studies reporting targeted therapy–induced pigmentary changes. The incidence and relative risk were calculated. Case reports and series were reviewed to understand clinical characteristics.

Results

A total of 8052 patients from 36 clinical trials were included. The calculated overall incidences of targeted cancer therapy–induced all-grade pigmentary changes in the skin and hair were 17.7% (95% confidence interval [CI], 11.9-25.4) and 21.5% (95% CI, 14.9-30.1), respectively. The relative risk of all-grade pigmentary changes of skin and hair were 93.7 (95% CI, 5.86-1497.164) and 20.1 (95% CI, 8.35-48.248). Across 53 case reports/series (N = 75 patients), epidermal growth factor receptor and breakpoint cluster region–abelson inhibitors were the most common offending agents.

Limitations

Potential under-reporting and variability in oncologists reporting these events.

Conclusion

There is a significant risk of development of pigmentary changes during treatment with targeted anticancer therapies. Appropriate counseling and management are critical to minimize psychosocial impairment and deterioration in quality of life.

The full text of this article is available in PDF format.

Key words : cabozantinib, depigmentation, dyspigmentation, hyperpigmentation, hypopigmentation, imatinib, ipilimumab, nivolumab, pazopanib, pembrolizumab, pigmentary, repigmentation, sorafenib, sunitinib, vitiligo

Abbreviations used : AE, Bcr-abl, BSA, CI, dpAE, RR, RCT



 Supported in part by the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P20 CA008748. Drs Lacouture and Belum are supported by the RJR Oncodermatology Fund. Funders and sponsors were not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.
 Disclosure: Dr Wu has speaking arrangements with Novartis, Bayer-Onyx, Pfizer, and Mediavation. Dr Sibaud has a speaking, consultant, or advisory role with Roche, GlaxoSmithKline, Pierre Fabre, Merck, Bristol-Myers Squibb, Bayer, and Boehringer Ingelheim. Dr Lacouture has a speaking, consultant, or advisory role with Abbvie, Quintiles, Boehringer Ingelheim, AstraZeneca Pharmaceuticals, Legacy Healthcare, Foamix, Adgero Bio Pharmaceuticals, Janssen R&D, Novartis, and Novocure; in addition, he receives research grants from Berg and Bristol-Myers Squibb. Drs Dai and Belum have no conflicts of interest to declare.
 Reprints not available from the authors.



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