New targets and drugs in prostate cancer Cora N. Sternberg, MD, FACP Chairman, Department of Medical Oncology San Camillo and Forlanini Hospitals Rome...
New targets and drugs in prostate cancer Cora N. Sternberg, MD, FACP Chairman, Department of Medical Oncology San Camillo and Forlanini Hospitals Rome, Italy
Castration Resistant Prostate Cancer (CRPC) • Has our perception of CRPC changed with the advent of more effective therapies?
• How has our increasing knowledge about the importance of the androgen receptor (AR) in the progression of prostate cancer helped us? • Have we commuted a death sentence into a more chronic disease that patients can learn to live with?
Time-line for Prostate Cancer Therapeutics Orchiectomy Shalley* Flutamide DES Nilutamide Huggins* LHRH Castration Bicalutamide agonists
Challenges to developing new drugs for advanced prostate cancer • Regulatory authorities: survival is the only accepted measure of outcome (no surrogate endpoints) • Castration Resistant rather than Hormone Refractory • Inter-patient molecular heterogeneity - ETS gene rearrangements (40-70%) - PTEN loss cancers (> 50%) - RAF rearrangements (~5%) - BRCA carrier cancers (5 to 26 (21.4 to ------) 21.3 (18.4 to ------) 9.3 ( 8.2 to 11.3) 6.8 ( 5.8 to 10.3)
N (%) 88 (38%) 45 (20%) 26 (11%) 71 (31%)
80% 70% 60%
1
50% 40% 30% 20% 10%
Curve Comparison 1 vs. 2 1 vs. 3 1 vs. 4 2 vs. 3 2 vs. 4 3 vs. 4
21.3m 4
*p-values not adjusted for multiple hypothesis tests