Cabazitaxel or mitoxantrone with prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: Final results of a multinational phase III trial (TROPIC). (2010)

4508^ Background: The treatment of mCRPC following docetaxel (D) therapy failure due to progressive disease (PD) or toxicity is an unmet medical need. TROPIC evaluated the efficacy and safety of the novel taxane cabazitaxel (Cbz) in men with mCRPC previously treated with D. Methods: Men with mCRPC, ECOG PS 0–2, and adequate organ function who had prior hormone therapy, chemotherapy, and radiotherapy, but had PD during or after D (cumulative dose ≥225 mg/m2) were randomized to 10 mg/day of prednisone with either mitoxantrone 12 mg/m2 (MP) or Cbz 25 mg/m2 (CbzP), both administered 3-weekly. The primary endpoint was overall survival (OS). Secondary endpoints were progression- free survival (PFS- composite of tumor, PSA, or pain progression; or death); response; time to progression (TTP) for tumor, PSA, pain; and safety. The study had 90% power to detect a 25% lower hazard rate for death in the CbzP group after 511 events (2-sided α= 0.05). Results: From Jan 2007 to Oct 2008, 755 men (median age 68 yr; 84% white) were randomized. Patients' characteristics were well balanced. Median prior D dose was 576 mg/m2 for CbzP and 529 mg/m2 for MP. Median follow-up was 12.8 mos. Median number of cycles was 6 for CbzP and 4 for MP. In the primary ITT analysis, the CbzP group had a statistically significantly longer OS compared with MP (p<0.0001). PFS, response rates, and TTP (by RECIST and PSA) also statistically significantly favored CbzP. Subgroup analyses by risk factors and a multivariate analysis showed that OS outcomes were consistent and robust in favor of CbzP. Most frequent Gr 3/4 toxicity was neutropenia (81.7% CbzP; 58.0% MP); rates of febrile neutropenia were 7.5% and 1.3%, respectively. Conclusions: Men with mCRPC progressing after D benefit from CbzP treatment with longer OS, TTP by tumor assessments and PSA, and higher response rates. Population MP CbzP CbzP vs. MP N (%) Median OS (mos) N (%) Median OS (mos) HR (95%CI) ITT 377 (100) 12.7 378 (100) 15.1 0.70 (0.59–0.83) PD while on D 103 (27) 12.0 113 (30) 14.2 0.65 (0.47–0.90) PD after last D dose <3 mos 180 (48) 10.3 158 (42) 13.9 0.70 (0.54–0.90) ≥3 mos 91 (24) 17.7 103 (27) 17.5 0.78 (0.53–1.14) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.