| General information |
| Database: | DB00207 |
| Objective: | Cabozantinib Smalate is a vascular endothelial growth factor receptor 2, cMET, 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. |
| Authors: | Zuo RC, et al |
| Title: | Cutaneous adverse effects associated with the tyrosinekinase inhibitor cabozantinib |
| Journal: | JAMA Dermatol. |
| Year: | 2015 |
| PMID: | 25427282 |
| Trial Design |
| Clinical Trial Id: | NCT01688999 |
| Agent: | cabozantinib
|
| Target: | Hepatocyte growth factor receptor, Vascular endothelial growth factor receptor 2
|
| Cancer Type: | Urothelial Carcinoma |
| Cancer Subtype: | advanced urothelial carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabel, nonrandomized, phase II clinical trial |
| Key Patients Feature: | 41 consecutive adults with metastatic, progressive urothelial carcinoma enrolled in a National Cancer Institute |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | 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.A detailed history, fullbody physical examination, and clinical photographs of cutaneous lesions were obtained. |
| Primary End Point: | skin reactions |
| Secondary End Point: | NA |
| Patients Number: | 41 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | 30 (73%) developed 1 or more cutaneous toxic effects. Adverse events included handfoot 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: | 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. |