The new FDA-approved agents all have varied biologic mechanisms of action. For this reason, more in depth study is needed to learn about prostate cancer biology. Thanks to the Prostate Tumor Board for its performance of bone biopsies, in many sites, to help better understand this biology. Currently, we don’t commonly see bone scan response so it’s important to understand what is going on with MET and VEGFR in tumor-bone infections.
Antiangiogenic studies of cabozantinib (a multikinase inhibitor that targets VEGFR2 and MET) was reported on a phase II randomized discontinuation trial with 103 patients with bone metastatic CRPC. In this patient cohort, 3 patients (3%) had new lesions on bone scan, 23 (21%) were stable, 61 (56%) had partial resolution, and 21 (19%) had complete resolution of all lesions. The dramatic effects on bone scans correlated with improvement in bone pain and bone turnover markers (i.e., alkaline phosphatase and C-telopeptide) but not prostate- specific antigen (PSA). This is a notable finding. Now studies of cabozantinib are moving into phase III trials.
Of interest is clusterin; it functions as a cytoprotective chaperone with increased expression in higher Gleason prostate cancer and CRPC. Clusterin may enhance the efficacy of anticancer therapies. Initial studies of clusterin have led to the SYNERGY trial, a randomized 800 mCRPC patient study comparing first-line docetaxel, prednisone, and custirsen versus docetaxel and prednisone. The endpoint of this trial is overall survival.
According to Dr. Yu, the next challenge is to perform reverse translation to better understand issues of heterogeneity and identify predictive biomarkers. He adds, “these efforts will allow us to optimize timing and selection of therapy in a rational manner.”
Presented by Evan Y. Yu, MD1 at the 2012 Genitourinary Cancers Symposium - February 2 - 4, 2012 - San Francisco Marriott Marquis - San Francisco, California
1University of Washington, Seattle, WA
Reported for UroToday by Karen Roberts, Medical Writer
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