Endocrine Abstracts

Background: Vandetanib and Cabozantinib are the only two multitarget tyrosine kinase inhibitors approved for the management of metastatic and progressive medullary thyroid cancer. (MTC) Despite their efficacy in terms of progression free survival prolongation and overall response rate, the drug-related toxicity is still a clinical problem, impairing patient’s quality of life and the compliance to the treatment. We retrospectively evaluate the adverse events (AEs) occurred during cabozantinib treatment in patient enrolled in the EXAM and EXAMINER clinical trial.

Matherials and Methods: We retrospectively analyzed data from 23 patients with metastatic MTC, follow-up at our department and enrolled in clinical trials with cabozantinib for radiological documented progression of disease. During follow-up a periodically clinical assessment and of tumoral markers (calcitonin and CEA) and hormonal-hematochemical parameters were performed every month, while a radiological assessment with total body CT scan with iodine contrast medium injection every 12 weeks. The clinical evaluation of AEs was performed according to the CTCAE (National Cancer Institute’s Common Terminology Criteria for Adverse Events) dictionary.

Results: All patients experienced AEs during treatment, which were classified in laboratoristic (endocrine and not) and clinical ones. The most frequent endocrine AEs observed were hypothyroidism (78.3%), hypocalcemia (47.8%), high levels of ACTH (34.8%) and FSH/lH. The most frequent not endocrine laboratoristic AEs occurred were AST/ALT high levels (82.6%), increasing in amylase and lipase enzyme (39.1%), renal impairment (21.7%), electrolyte n (43.5%), hematological (60.9%) and coagulation (21.7%) alterations. None of endocrine and not endocrine AEs caused drug stopped or dose reduction since they were well managed with supporting therapies. The most frequent clinical AEs observed were gastrointestinal as mucositis (82.6%), diarrhea (73.9%), nausea/vomiting (34.8%), dysgeusia (30.4%), epigastralgy (26.1%), dysphagia (21.7%); thereafter, constitutional AEs as anorexia (21.7%) and weight loss (47.8%) and cutaneous AEs (47.8%). These AEs occurred early after the drug initiation and, despite preventing and supporting therapies, they were the main cause of drug withdrawal and dose reduction. The analysis of which AE could be a predicting factor of response in still ongoing.

Conclusions: Cabozantinib is an effective treatment for MTC patients. However, AEs occur in all patients during follow-up, but while the laboratoristic ones appear later and are well manageable, the clinical ones occur early and are the main responsible for dose reduction and discontinuation, impair patient’s quality of life and disease control. The knowledge, prevention and early treatment of these AEs are fundamental for patients’ compliance.