New targets and drugs in prostate cancer

New targets and drugs in prostate cancer Cora N. Sternberg, MD, FACP Chairman, Department of Medical Oncology San Camillo and Forlanini Hospitals Rome...
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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

Mitoxantrone Docetaxel Zoledronic acid Sipuleucel-T Cabazitaxel Denosumab (FDA)

CRPC 19401950

19601980

19771990

* Nobel Prize in 1966

1989

1997 1999

20022006

2010

Challenges to developing new drugs for advanced prostate cancer

Bone metastases are difficult to evaluate

Skeletal-related events (SREs) Pathologic Fracture

Radiotherapy to Bone

Surgery to Bone

Spinal Cord Compression

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

0%

Group 1 Group 2 Group 3 Group 4

Logrank p-Value* 0.1528