Quale sarà il ruolo di Denosumab: la 1° linea di trattamento, l’associazione all’ac. zolendronico o la 2° linea ?

G. CartenìDirettore U.O.S.C. di Oncologia Medica A.O.R.N.A. Cardarelli Napoli

GESTIONE DELLE METASTASI OSSEE

Skeletal Complication Risk: Incremental Benefits in Prostate

Cancer

No bisphosphonate 49% risk at 2 yrs

Zoledronic ~ 20% risk reduction Denosumab

Additional ~ 12% risk reduction

Denosumab Additional 18%

time to first SRE increase

Saad F, JNCI, 2004, Fizazi K, Lancet, 2011

+

Abiraterone post-docetaxel does delay SREs

Logothetis et al. Lancet Oncology, 2012

4.7 months of difference

JS De Bono, ASCO, 2012

Enzalutamide post-docetaxel does delay SREs

3.4 months of difference

Pre-planned analysis

Direct Androgen dependent Interactions in Bone disease

Hypothetic interactions.

Stroma

> Angiogenesis

Osteoblast

Tumor Cell

Osteoclast

Migrationproliferation

survival

> apoptosis

Migrationproliferation

survival

Wiren KM, Bone, 2006; Eisermann K, Mol Cancer, 2013

ANDROGEN

Dayyani F et al. JNCI J Natl Cancer Inst 2011;103:1665-1675

Inhibition of androgen pathway in cancer cells and indirect

effects on microenvironment