Cyclin-Dependent Kinase 4/6 Inhibitors and Dermatologic Adverse Events: Results from the EADV Task Force "Dermatology
Pietro Sollena1, Nikolaou Vasiliki2, Elias Kotteas3
1UOC Dermatologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Background:
The introduction of cyclin-dependent kinase inhibitors (CDK4/6i) was a great advance in therapeutics for patients with estrogen receptor+/human epidermal growth factor receptor (HER2) locally advanced and metastatic breast cancer. Despite the increasing use of these agents, their adverse drug-related events have not yet been fully characterized. We describe the spectrum of cutaneous adverse reactions occurring in advanced breast cancer patients treated with cyclin-dependent kinase inhibitors, analyzing types, severity, time to onset, and possible treatment outcomes.
Methods:
We performed a multicentric retrospective study including patients with advanced breast cancer who developed cutaneous lesions during treatment with CDK4/6i in the period from June 2020 to June 2021. Patients > 18 years were recruited at eleven onco-dermatology units located in Albania (1), Argentina (1), France (1), Greece (3), Italy (3), and Spain (2). We evaluated patients' epidemiological and clinical characteristics, types of cutaneous adverse events, their time to onset, and treatment outcomes. The severity of the skin reactions was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 score.
Results:
Seventy-nine patients (median age: 62.3 years; range 39-83 years) were included in the study, and, collectively, we recorded a total of 165 cutaneous adverse events during follow-up visits. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and eczematous lesions (24/79). Cutaneous toxicities were usually mild in severity (>65%) and occurred after a median of 6.5 months. Only four patients (5%) required treatment discontinuation due to the severity of the skin lesions. The majority of the skin reactions were managed with topical treatments.
Conclusions:
To the best of our knowledge, we present the largest case series of cutaneous adverse events developing in advanced breast cancer patients treated with CDK4/6i. We showed that cutaneous toxicities are usually mild in severity, and manageable with standard supportive care; however, in selected cases, they can lead to treatment discontinuation with possible implications for patients' clinical outcomes.
Insights
Cyclin-dependent kinase inhibitors (CDK4/6i) treat advanced breast cancer but can cause skin reactions. Most cutaneous adverse events are mild and manageable with topical treatments, rarely requiring therapy discontinuation.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Cyclin-dependent kinase inhibitors (CDK4/6i) are crucial for estrogen receptor-positive, HER2-negative advanced breast cancer.
- Characterizing adverse drug reactions, particularly cutaneous events, is essential for optimizing CDK4/6i therapy.
- This study addresses the spectrum of skin reactions associated with CDK4/6i in advanced breast cancer patients.
Purpose of the Study:
- To describe the types, severity, and onset of cutaneous adverse reactions in patients receiving CDK4/6i.
- To analyze treatment outcomes and management strategies for these skin toxicities.
- To contribute to a comprehensive understanding of CDK4/6i-related dermatologic side effects.
Main Methods:
- A multicentric retrospective study involving 79 advanced breast cancer patients treated with CDK4/6i.
- Data collected from eleven onco-dermatology units between June 2020 and June 2021.
- Cutaneous adverse events assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0, with analysis of clinical characteristics and outcomes.
Main Results:
- 165 cutaneous adverse events were recorded, with pruritus, alopecia, and eczematous lesions being most frequent.
- Over 65% of toxicities were mild, with a median onset of 6.5 months.
- Only 5% of patients discontinued treatment due to skin reactions; most were managed with topical therapies.
Conclusions:
- This series represents the largest documented cohort of cutaneous adverse events in advanced breast cancer patients on CDK4/6i.
- CDK4/6i-induced skin toxicities are generally mild and manageable with supportive care.
- While typically manageable, severe skin reactions can necessitate treatment discontinuation, potentially impacting patient outcomes.
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