Management of Adverse Events Associated with Cabozantinib Treatment in Patients with Advanced Hepatocellular Carcinoma.

Cabozantinib is an oral multikinase inhibitor whose targets include vascular endothelial growth factor receptors, MET, and the TAM family of kinases (TYRO3, AXL, MER). Cabozantinib is approved for patients with advanced hepatocellular carcinoma who have been previously treated with sorafenib, based on improved overall survival and progression-free survival relative to placebo in the phase III CELESTIAL study. During CELESTIAL, the most common adverse events (AEs) experienced by patients receiving cabozantinib included palmar-plantar erythrodysesthesia, fatigue, gastrointestinal-related events, and hypertension. These AEs can significantly impact treatment tolerability and patient quality of life. However, AEs can be effectively managed with supportive care and dose modifications. During CELESTIAL, more than half of the patients receiving cabozantinib required a dose reduction, while the rate of treatment discontinuation due to AEs was low. Here, we review the safety profile of cabozantinib and provide guidance on the prevention and management of the more common AEs, based on current evidence from the literature as well as our clinical experience. We consider the specific challenges faced by clinicians in treating this patient population and discuss factors that may affect exposure and tolerability to cabozantinib.

Risk of differentiated thyroid carcinoma and polymorphisms within the susceptibility cancer region 8q24.

BACKGROUND: Genome-wide association studies have shown that the 8q24 region harbours multiple independent cancer susceptibility loci and it was also defined as the "susceptibility cancer region." Thus, it could be hypothesized that genetic variants within this region could play a role in the risk of differentiated thyroid carcinoma (DTC). METHODS: Six single-nucleotide polymorphisms within 8q24 were analyzed, previously associated with the risk of cancer (i.e., rs6983267, rs1447295, rs10808556, rs7000448, rs13254738, and rs13281615) in a population of 1,250 patients affected by DTC and 1,250 controls from Central and Southern Italy. RESULTS: A strong association between smoking habit and risk of DTC was found [OR, 1.63; 95% confidence interval (CI), 1.39-1.91; P < 10(-6)]. The polymorphisms rs10808556 and rs1447295 showed an association with the risk of DTC (the strongest were the heterozygotes with OR, 1.38; 95% CI, 1.13-1.68 and OR, 1.35; 95% CI, 1.02-1.78, respectively), but, overall, they were unable to reach the statistically significant threshold following Bonferroni's correction. CONCLUSIONS: Present study suggested a limited involvement of polymorphisms within 8q24 region in relation to the risk of DTC in Central and Southern Italians. IMPACT: The exclusion of a relationship between DTC and 8q24 among Italians further highlights the tissue-specificity of this chromosomal segment in relation to human cancer and stresses the importance of other population-specific cofactors.