title: Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma.
abstract: BACKGROUND
  A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma.
  
  
  METHODS
  Patients received cabozantinib 100 mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation progression-free survival (PFS).
  
  
  RESULTS
  Seventy-seven patients were enroled (62% cutaneous, 30% uveal, and 8% mucosal). At week 12, the ORR was 5%; 39% of patients had SD. During the lead-in phase, reduction in target lesions from baseline was seen in 55% of evaluable patients overall and in 59% of evaluable patients with uveal melanoma. Median PFS after randomisation was 4.1 months with cabozantinib and 2.8 months with placebo (hazard ratio of 0.59; P=0.284). Median PFS from study day 1 was 3.8 months, 6-month PFS was 33%, and median overall survival was 9.4 months. The most common grade 3/4 adverse events were fatigue (14%), hypertension (10%), and abdominal pain (8%). One treatment-related death was reported from peritonitis due to diverticular perforation.
  
  
  CONCLUSIONS
  Cabozantinib has clinical activity in patients with metastatic melanoma, including uveal melanoma. Further clinical investigation is warranted.
authors.affiliation: University of California, San Francisco Medical Center at Parnassus, 1600 Divisadero Street, MZ Bldg A, San Francisco, CA 94115, USA.
authors.forename: Adil
authors.initials: A
authors.lastname: Daud
authors.affiliation: Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, PO Box 208028, New Haven, CT 06520-8028, USA.
authors.forename: Harriet M
authors.initials: HM
authors.lastname: Kluger
authors.affiliation: University of California, San Diego Moores Cancer Center, 3855 Health Sciences Drive, MC #0658, La Jolla, CA 92093-0658, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Exelixis Inc., 210 E. Grand Avenue, South San Francisco, CA 94080, USA.
authors.forename: Frauke
authors.initials: F
authors.lastname: Schimmoller
authors.affiliation: Exelixis Inc., 210 E. Grand Avenue, South San Francisco, CA 94080, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Weitzman
authors.affiliation: Department of Hematology/Oncology, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd, Weston, FL 33331, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Samuel
authors.affiliation: Cancer Care Associates, 1810 E 15th Street, Tulsa, OK 74104, USA.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Moussa
authors.affiliation: Pinnacle Oncology Hematology, 9055 E. Del Camino, Suite 100, Scottsdale, AZ 85258, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Early Drug Development Center, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: Shapiro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001530:Belgium / Q000453:epidemiology; D005260:Female; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D028761:Withholding Treatment / Q000706:statistics & numerical data; D000098943:Uveal Melanoma
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D011725:Pyridines; C558660:cabozantinib; D019859:Proto-Oncogene Proteins c-met; D040262:Receptors, Vascular Endothelial Growth Factor