Investigational agent improves progression- free survival in advanced prostate cancer

August 1, 2011

Use of the investigational tyrosine kinase inhibitor (TKI) cabozantinib led to complete or partial resolution of radionuclide tracer uptake by bone scan in three-fourths of men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastasis in an international phase II randomized discontinuation trial.

Chicago-Use of the investigational tyrosine kinase inhibitor (TKI) cabozantinib led to complete or partial resolution of radionuclide tracer uptake by bone scan in three-fourths of men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastasis in an international phase II randomized discontinuation trial.

First author Maha Hussain, MD, presented updated interim data from the trial at the American Society of Clinical Oncology annual meeting in Chicago.

Cabozantinib is a dual inhibitor of MET and vascular endothelial growth factor receptor 2 (VEGFR2). MET is upregulated in many tumor types and promotes tumor cell invasion and metastasis; preclinically, androgen deprivation increases MET expression, and increased expression of MET is observed in tissues from prostate cancer bone metastases. Both MET and the VEGFR2 signaling pathways appear to direct crosstalk between tumor cells, osteoblasts, and osteoclasts, said Dr. Hussain, associate director for clinical research at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Randomization after the 12-week lead-in phase was suspended after 122 patients based on the observed clinical activity of cabozantinib; 79 men entered the open-label extension phase and 31 with stable disease entered the randomized portion of the trial. The disease control rate (no tumor progression consisting of stable disease and partial response) at week 12 was 68%.