ASCO 2014. LBA 2. Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial.
Christopher Sweeney, Yu-Hui Chen, Michael Anthony Carducci, Glenn Liu, David Frasier Jarrard, Mario A. Eisenberger, Yu-Ning Wong, Noah M. Hahn, Manish Kohli, Nicholas J. Vogelzang, Matthew M. Cooney, Robert Dreicer, Joel Picus, Daniel H. Shevrin, Maha Hussain, Jorge A. Garcia, Robert S. DiPaola; Dana-Farber Cancer Institute, Boston, MA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; University of Wisconsin Carbone Cancer Center, Madison, WI; Fox Chase Cancer Center, Philadelphia, PA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Mayo Clinic, Rochester, MN; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Cleveland Clinic, Cleveland, OH; Division of Oncology, Washington University in St. Louis, St. Louis, MO; NorthShore University HealthSystem, Evanston, IL; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Rutgers Biomedical and Health Sciences, New Brunswick, NJ
Background: Docetaxel (D) improves OS of men with mPrCa who have progressed on androgen deprivation therapy (ADT). We aimed to assess the benefit of upfront chemohormonal therapy for metastatic PrCa.
Methods: 1:1 randomization to ADT alone or ADT + D dosed 75mg/m2 every 3 weeks for 6 cycles within 4 month (mos) of starting ADT. Stratification factors: high volume (HV) vs. low volume (LV) disease (HV: visceral metastases and/or 4 or more bone metastases); anti-androgen use beyond 30 days; Age ≥70 vs. < 70 years; ECOG PS 0-1 vs. 2; Prior adjuvant ADT > 12 vs. ≤ 12 mos; FDA approved drug for delaying skeletal related events. Key eligibility criteria: suitable organ and neurological function for D; adjuvant ADT ≤ 24 mos and no progression within 12 mos of adjuvant ADT. OS was the primary endpoint and the study was powered to assess for a 33.3% improvement in median OS (80% power and 1-sided alpha=2.5%). Projected median OS for ADT alone: HV-33 mos; LV-67 mos.
Results: 790 men were accrued from 7/28/06 to 11/21/2012: ADT N=393; ADT + D: N=397; balanced for demographic, stratification and disease factors. Median age: 63 years (range: 36 to 91); 98% ECOG PS 0 or 1; 89% Caucasian; 24% prior radiotherapy, 24% prior prostatectomy; HV 64% on ADT and 67% on ADT + D. Data released after 4th interim analysis in Sept 2013 when O’Brien Fleming upper boundary was crossed with 53.1% information. This report reflects 1/16/2014 data with median follow-up of 29 mos with 137 deaths on ADT alone vs. 104 deaths on ADT+D. ADT+D: Grade (G) 3/4 Neutropenic fever: 4%/2%; G3 neuropathy: 1% sensory, 1% motor; 1 death due to treatment (no deaths due to treatment on ADT). Efficacy data is in the table below. After disease progression, 123 pts on ADT alone and 45 pts on ADT + D received docetaxel.
Conclusions: ADT + D improves OS over ADT alone in men with HV mPrCa. Longer follow-up is needed for men with LV mPrCa.