Cutaneous adverse effects associated with the tyrosine-kinase inhibitor cabozantinib
Rena C Zuo1, Andrea B Apolo2, John J DiGiovanna1
1Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Importance:
Cabozantinib S-malate is a vascular endothelial growth factor receptor 2, c-MET, and RET multitargeted tyrosine kinase inhibitor that has antiangiogenic and antitumorigenic properties with potential efficacy for the treatment of several cancers. Cutaneous reactions, one of the most frequently observed adverse effects associated with tyrosine kinase inhibitors, can significantly affect patients' quality of life and drug adherence and represent a major therapeutic challenge to maximizing the efficacy of targeted cancer therapy.
Objective:
To describe the frequency and spectrum of skin reactions in patients with urothelial carcinoma receiving cabozantinib as monotherapy.
Design, Setting, And Participants:
A single-institution study at the Clinical Research Center at the National Institutes of Health included 41 consecutive adults with metastatic, progressive urothelial carcinoma enrolled in a National Cancer Institute open-label, nonrandomized, phase 2 clinical trial. Patients receiving cabozantinib were evaluated for the development of skin reactions at each treatment visit from October 2012 to June 2014 by the primary oncology team and referred for dermatologic evaluation as appropriate.
Main Outcomes And Measures:
A detailed history, full-body physical examination, and clinical photographs of cutaneous lesions were obtained.
Results:
Of 41 consecutive patients who received cabozantinib, 30 (73%) developed 1 or more cutaneous toxic effects. Adverse events included hand-foot skin reaction (22 [54%]), generalized pigment dilution and/or hair depigmentation (18 [44%]), xerosis (8 [20%]), scrotal erythema/ulceration (6 [15%]), and nail splinter hemorrhages (5 [12%]). Eighteen patients (44%) had 2 or more cutaneous adverse events. Reactions developed in 17 of 30 patients (57%) during the first month of cabozantinib treatment and in 24 of 30 (80%) by the second month. Of patients with skin toxic effects, dose reduction was required for symptom management in 9 of 30 patients (30%), and treatment discontinuation was required in 4 of 30 (13%).
Conclusions And Relevance:
Cabozantinib monotherapy is associated with 1 or more cutaneous adverse events in most patients. Early detection and prompt treatment may increase patients' adherence to tyrosine kinase inhibitor therapy.
Trial Registration:
clinicaltrials.gov Identifier: NCT01688999.
Insights
Most patients (73%) receiving cabozantinib for urothelial carcinoma experienced skin reactions, including hand-foot syndrome and hair depigmentation. Early detection and treatment are key for adherence to this cancer therapy.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Cabozantinib S-malate is a multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumorigenic properties.
- Cutaneous reactions are common adverse effects of tyrosine kinase inhibitors, impacting patient quality of life and treatment adherence.
- Understanding these reactions is crucial for managing targeted cancer therapies.
Purpose of the Study:
- To determine the frequency and spectrum of skin reactions in patients with urothelial carcinoma treated with cabozantinib monotherapy.
- To evaluate the impact of cutaneous toxicities on treatment management.
Main Methods:
- A phase 2, single-institution clinical trial involving 41 adults with metastatic urothelial carcinoma.
- Patients received cabozantinib monotherapy and were monitored for skin reactions by oncology and dermatology teams.
- Data collection included patient history, physical examinations, and clinical photographs.
Main Results:
- 73% of patients (30/41) developed at least one cutaneous adverse event.
- Common reactions included hand-foot skin reaction (54%), pigment/hair changes (44%), xerosis (20%), and scrotal erythema/ulceration (15%).
- Most reactions occurred within the first two months; 30% required dose reduction and 13% required treatment discontinuation.
Conclusions:
- Cabozantinib monotherapy frequently causes cutaneous adverse events in urothelial carcinoma patients.
- Prompt dermatologic evaluation and management are essential for maintaining treatment adherence and maximizing therapeutic efficacy.
- Further research into managing TKI-induced skin toxicities is warranted.
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