title: Cabozantinib for the treatment of progressive metastatic medullary thyroid cancer.
abstract: Cabozantinib (XL-184) is a potent inhibitor of MET, VEGFR 2/KDR, RET and other receptor tyrosine kinases, such as KIT, AXL and FLT3. Its efficacy against MTC has been demonstrated in a prospective, randomized, placebo-controlled study (EXAM). Cabozantinib comparing to placebo significantly prolonged progression free survival both in hereditary and sporadic MTC, 11.2 vs 4.0 months, respectively. Final analysis showed no global differences in overall survival (OS) between cabozantinib and placebo. However, in a subgroup with RET M918T mutation the difference in OS was significant: 44.3 vs 18.9 months, respectively. Among the most frequent cabozantinib-related adverse events (AEs), observed in >30% of patients were diarrhea, palmar-plantar erythrodysesthesia, decreased weight, decreased appetite, nausea, fatigue, dysgeusia, hair color changes and hypertension. Expert Commentary: Cabozantinib constitutes an effective treatment option with acceptable toxicity in MTC patients showing either germinal or sporadic tumor RET M918T mutation as the drug prolonged OS in these subjects.
authors.affiliation: a Nuclear Medicine and Endocrine Oncology Department , M.Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Gliwice , Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Krajewska
authors.affiliation: a Nuclear Medicine and Endocrine Oncology Department , M.Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Gliwice , Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Olczyk
authors.affiliation: a Nuclear Medicine and Endocrine Oncology Department , M.Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Gliwice , Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Jarzab
mesh_terms: D000813:Anilides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C558660:cabozantinib; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: RET M918T mutation; TKI; VEGFR inhibitor; cabozantinib; medullary thyroid cancer