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Br J Cancer. 2017 Feb 14;116(4):432-440. doi: 10.1038/bjc.2016.419. Epub 2017 Jan 19.

Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma.

Author information

1
University of California, San Francisco Medical Center at Parnassus, 1600 Divisadero Street, MZ Bldg A, San Francisco, CA 94115, USA.
2
Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, PO Box 208028, New Haven, CT 06520-8028, USA.
3
University of California, San Diego Moores Cancer Center, 3855 Health Sciences Drive, MC #0658, La Jolla, CA 92093-0658, USA.
4
Exelixis Inc., 210 E. Grand Avenue, South San Francisco, CA 94080, USA.
5
Department of Hematology/Oncology, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd, Weston, FL 33331, USA.
6
Cancer Care Associates, 1810 E 15th Street, Tulsa, OK 74104, USA.
7
Pinnacle Oncology Hematology, 9055 E. Del Camino, Suite 100, Scottsdale, AZ 85258, USA.
8
Department of Medical Oncology, Dana-Farber Cancer Institute, Early Drug Development Center, 450 Brookline Avenue, Boston, MA 02215, USA.

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.

PMID:
28103611
PMCID:
PMC5318966
DOI:
10.1038/bjc.2016.419
[Indexed for MEDLINE]
Free PMC Article

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