946 - Cabazitaxel (CBZ) shows superior antitumor efficacy over docetaxel in a hormone-resistant prostate tumor xenograft model (HID28)

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anti-Cancer Agents & Biologic Therapy
Basic Science
Prostate Cancer
Presenter Ludovic Bourré
Authors L. Bourré1, D. Nicolle1, M. Legrier2, V. Yvonnet3, J. Charpentier3, M. Poupon4, P. Vrignaud5, S. Oudard6, J. Judde3
  • 1Contract Research Department, XenTech, 91000 - Evry/FR
  • 2R & D, XenTech, 91000 - Evry/FR
  • 3N/a, XenTech, 91000 - Evry/FR
  • 4Scientific Advisory Board, XenTech, 94260 - Fresnes/FR
  • 5Translational And Experimental Medicine, Sanofi Oncology, 94400 - Vitry-sur-Seine/FR
  • 6Medical Oncology Service, Hopital Europeen Georges Pompidou, 75015 - Paris/FR

Abstract

Background

Docetaxel (D) was the first cytotoxic treatment demonstrating a survival benefit in metastatic castration-resistant prostate cancer (mCRPC) patients. Recently, the novel taxane cabazitaxel and the CYP17 inhibitor abiraterone acetate have demonstrated a significant survival benefit in mCRPC patients progressing after receiving a D-containing regimen. Here we compare the antitumour efficacy of D, cabazitaxel and abiraterone acetate in the HID28 hormone-resistant human prostate carcinoma xenograft.

Methods

HID28 tumour-bearing nude mice received 20 mg/kg of D (IP, Q3W x 2), cabazitaxel at 15 and 20 mg/kg (IP, Q3W x 2) and abiraterone acetate at 50 mg/kg (PO, QD x 21). Median tumour growth inhibition (T/C%) was evaluated, as well as time-course androgen receptor expression (4, 8 and 24 h post-dosing) by western blot analysis.

Results

D inhibited tumour growth with a T/C% = 16.7% at day 35, 2 partial (PR) and 1 complete (CR) tumour regressions, and with relapse of all tumours (3/3) observed at day 42. Cabazitaxel demonstrated dose-dependent efficacy at day 35 with T/C% = 10.8% and 1.4% for 15 and 20 mg/kg doses, respectively. At a cabazitaxel dose of 15 mg/kg, 4/10 PR and 3/10 CR were observed, whereas 4/10 PR and 6/10 CR were observed at 20 mg/kg. At day 42, 6/6 tumour relapses were observed at 15 mg/kg, whereas only 3/6 relapses were observed at 20 mg/kg. No anti-tumour activity was demonstrated with abiraterone acetate as well as no significant decreases in testosterone levels compared with the vehicle group. Tolerability was good for all treatment groups, with a transitory maximum mean body weight loss of 12%, 6 days after treatments.

Androgen receptor western blot expression analysis after 4, 8 and 24 h post-dosing demonstrated no significant difference between groups and over time.

Conclusions

Cabazitaxel demonstrated superior antitumour efficacy and a similar tolerability compared with D at equivalent dosing in the HID28 hormone-resistant tumour model. The model did not respond to abiraterone. These results support the clinical development of cabazitaxel in first-line treatment of mCRPC patients.

This research was funded by Sanofi.

Disclosure

L. Bourré: Is a Xentech employee,

D. Nicolle: Is a Xentech employee,

M. Legrier: Is a Xentech employee,

V. Yvonnet: Is a Xentech employee,

J. Charpentier: Is a Xentech employee,

M. Poupon: Has acted as an uncompensated consultant and has provided expert testimony. Is a Xentech employee,

P. Vrignaud: Is a Sanofi employee (Research Investigator) and owns Sanofi stocks and shares,

S. Oudard: Has acted as an advisor for, and received honoraria from Pfizer Oncology, Bayer Schering Pharma, Roche, GSK, Novartis and Sanofi,

J-G. Judde: Is a Xentech employee.