Dermatologic toxicities to inhibitors of cyclin-dependent kinases CDK 4 and 6: An updated review for clinical practice

Abstract

Cyclin-dependent kinase (CDK) 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have revolutionized the treatment of metastatic breast carcinoma. They currently form the first-line treatment, in combination with endocrine agents, for the management of locally advanced or metastatic hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, the largest subtype of breast carcinoma. CDK 4/6 inhibitors have shown comparable efficacy outcomes with predictable and manageable adverse events. In this setting, dermatologic toxicity appears to be relatively frequent, accounting for up to 15% of all reported adverse events. It is usually mild to moderate in intensity and does not normally constitute a dose-limiting toxicity. The range of dermatologic adverse events includes both non-specific entities (maculopapular rash, pruritus, alopecia) and more characteristic toxicities related to CDK4/6 inhibitors, such as vitiligo-like lesions or cutaneous lupus erythematosus. Finally, more severe or life-threatening skin reactions can occasionally occur. The main dermatologic manifestations associated with CDK4/6 inhibitors, as well as management thereof, are described in this comprehensive review.

Keywords: Acute generalized exanthematous pustulosis; Alopecia; Bullous dermatitis; Dysgeusia; Eczema-like; Lupus erythematosus; Pruritus; Radiation enhancement; Radiation recall; Rash; Stevens-Johnson syndrome; Stomatitis; Toxic epidermal necrolysis; Vitiligo; Xerosis.