901PD - Association of progression by Prostate Cancer Working Group (PCWG)-2 criteria and survival in metastatic castration resistant prostate cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Genitourinary tumors, prostate
Topics Prostate Cancer
Presenter Guru Sonpavde
Authors G. Sonpavde1, G.R. Pond2, A.J. Armstrong3, M.D. Galsky4, B.A. Wood5, S. Wang6, J. Paolini7, M. Lechuga8, M.R. Smith9, M..D. Michaelson10
  • 1Medical Oncology, Texas Oncology, Baylor College of Medicine, 77598 - Webster, TX/US
  • 2Biostatistics, Ontario Clinical Oncology Group and McMaster University, Hamilton/CA
  • 3Medical Oncology, Duke Comprehensive Cancer Center and the Duke Prostate Center, Durham/US
  • 4Medical Oncology, Mt. Sinai Tisch Cancer Institute, New York/US
  • 5Drug Development, Ascenta Therapeutics, Malvern/US
  • 6Statistics, Pfizer, Inc, New Jersey/US
  • 7Clinical Development, Pfizer, Inc, New Jersey/US
  • 8Drug Development, Pfizer, Inc, New Jersey/US
  • 9Hematology-oncology, Massachusetts General Hospital Cancer Center, Boston/US
  • 10Medical Oncology, Massachusetts General Hospital Cancer Center, Boston/US

 

Abstract

Background

Intermediate endpoints to identify active agents for metastatic castration-resistant prostate cancer (mCRPC) are suboptimal. The Prostate Cancer Working Group (PCWG)-2 guidelines recommend time to clinical or radiographic event endpoints, and discouraged use of endpoints using PSA changes. We investigated the association of progression defined by PCWG-2 guidelines and overall survival (OS).

Methods

Two trials were analyzed: CS-205, a randomized phase II trial (n = 221) comparing first-line docetaxel-prednisone (DP) plus AT-101 or placebo, and SUN-1120 (n = 873), a phase III trial comparing prednisone plus sunitinib (SP) or placebo (PP) following docetaxel-based chemotherapy. Both trials continued therapy until progression defined by PCWG-2 criteria and OS was the primary endpoint. OS was derived by the Kaplan-Meier method. Cox proportional hazards regression models were used to estimate the effect of progression on OS. Landmark analyses at 2-month intervals compared patients with prior progression with those without progression. Sub-analyses compared patients removed from trial for progression vs. other reasons and examined the association of type of progression with OS.

Results

Patients who had previously progressed had an increased risk of death. In CS-205, the hazards ratio (HR) ranged from 2.31 to 3.43 between landmark times of 6 to 12 months and in SUN-1120 HR was 2.75 to 5.21 between landmark times from 2 to 8 months. Median OS was 5.5 versus 14.4 months in CS-205 beyond month 6 and 7.1 versus 16.1 months in SUN-1120 beyond month 2 for those with/without prior progression. The types of progression associated with OS varied between the trials. Patients removed from study due to progression (excluding death) had a significantly worse OS than those coming off for other reasons (HR: 1.90, 95% CI: 1.26-2.87 in CS-205 and HR: 1.23, 95% CI: 1.02-1.48 in SUN-1120).

Conclusions

Progression by PCWG-2 criteria was significantly associated with decreased OS in patients receiving first-line docetaxel-based chemotherapy or post-docetaxel therapy. Further validation will facilitate the employment of PCWG-2 defined progression as an intermediate endpoint.

Disclosure

G. Sonpavde: Research support to institution from Ascenta Therapeutics and Pfizer, Inc,

B.A. Wood: Employee of Ascenta Therapeutics,

S. Wang: Employee of Pfizer, Inc,

J. Paolini: Employee of Pfizer, Inc,

M. Lechuga: Employee of Pfizer, Inc,

M.R. Smith: Research support to institution from Pfizer, Inc,

M.D. Michaelson: Research support to institution from Pfizer, Inc,

All other authors have declared no conflicts of interest.