1. Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma.
- Author
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Daud, Adil, Kluger, Harriet M, Kurzrock, Razelle, Schimmoller, Frauke, Weitzman, Aaron L, Samuel, Thomas A, Moussa, Ali H, Gordon, Michael S, and Shapiro, Geoffrey I
- Subjects
Humans ,Melanoma ,Uveal Neoplasms ,Skin Neoplasms ,Neoplasm Metastasis ,Anilides ,Pyridines ,Receptors ,Vascular Endothelial Growth Factor ,Antineoplastic Agents ,Withholding Treatment ,Survival Analysis ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,United States ,Israel ,Belgium ,Female ,Male ,Proto-Oncogene Proteins c-met ,cabozantinib ,metastatic melanoma ,uveal melanoma ,vascular endothelial growth factor receptor ,MET/VEGFR inhibitor ,bone metastases ,Receptors ,Vascular Endothelial Growth Factor ,and over ,Oncology & Carcinogenesis ,Oncology and Carcinogenesis ,Public Health and Health Services - Abstract
BackgroundA 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.MethodsPatients 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).ResultsSeventy-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.ConclusionsCabozantinib has clinical activity in patients with metastatic melanoma, including uveal melanoma. Further clinical investigation is warranted.
- Published
- 2017