Data from the 100 mg daily dose of cabozantinib in the CRPC NRE cohort were most recently presented in June 2012 at the American Society of Clinical Oncology (ASCO) 2012 Annual Meeting (Abstract #4513).
The Significance of Bone Metastases in CRPC
The primary cause of morbidity and mortality in patients with CRPC is metastasis to the bone, which occurs in about 90% of cases. Bone metastases cause local disruption of normal bone remodeling, with lesions generally showing a propensity for an osteoblastic (bone-forming) phenotype on imaging. These lesions often lead to increased skeletal fractures, spinal cord compression, and severe bone pain. Osteoblastic lesions are typically visualized in CRPC patients by bone scan, which detects rapid incorporation of 99mTc-labeled methylene-diphosphonate radiotracer into newly forming bone. In addition, increased blood levels of BSAP and CTx, markers for osteoblast and osteoclast activity, respectively, are often observed in CRPC patients with bone metastases, and are associated with shorter overall survival.
Cabozantinib inhibits MET and VEGFR2. Cabozantinib is an investigational agent that provides coordinated inhibition of metastasis and angiogenesis to kill tumor cells while blocking their escape pathways. MET is upregulated in many tumor types, thus facilitating tumor cell escape by promoting the formation of more aggressive phenotypes, resulting in metastasis. MET-driven metastasis may be further stimulated by hypoxic conditions in the tumor environment, which are often exacerbated by selective VEGF-pathway inhibitors. Exelixis submitted a new drug application (NDA) for cabozantinib as a treatment for patients with progressive, unresectable, locally advanced, or metastatic medullary thyroid cancer to the United States Food and Drug Administration. The Prescription Drug User Fee Act (PDUFA) action date for the NDA is November 29, 2012.
About The Institute of Cancer Research
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.