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 Anticancer agents
Cancer Biology
Prostate Cancer
Basic Scientific Principles
Therapy
Biological Therapy
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.