Plenary: Next Frontier, Sunday, Afternoon Session
Presentation Authors: James A. Eastham*, Glenn Heller, New York, NY, Susan Halabi, Durham, NC, J. Paul Monk, Columbus, OH, Himisha Beltran, New York, NY, Martin Gleave, Vancouver, Canada, Christopher P. Evans, Sacramento, CA, Steven K. Clinton, Columbus, OH, Russell Z. Szmulewitz, Chicago, IL, Jonathan Coleman, New York, NY, David W. Hillman, Rochester, MN, Colleen Watt, Olwen M. Hahn, Chicago, IL, Mary-Ellen Taplin, Boston, MA, Eric J. Small, San Francisco, CA, James Mohler, Buffalo, NY, Michael J. Morris, New York, NY
Introduction:Radical prostatectomy (RP) is a mainstay of treatment for men with clinically localized, high risk prostate cancer (CLHRPC). We assessed whether chemohormonal therapy with androgen deprivation therapy (ADT) plus docetaxel followed by RP would result in improved biochemical progression free survival (bPFS) than RP alone.
Methods: CALGB 90203 (Alliance) is a Phase III study which randomly assigned in a 1:1 fashion men with CLHRPC (biopsy Gleason Grade Group 4 or 5 or Kattan pre-op nomogram bPFS < 60%) to RP alone or RP plus neoadjuvant ADT plus docetaxel (75 mg per square meter of body-surface area every 3 weeks for 6 cycles). The primary objective was to test the hypothesis that 3-year bPFS would be longer in the neoadjuvant chemohormonal therapy arm. Secondary endpoints included overall bPFS and overall survival (OS). The events for the bPFS endpoint are progression, defined as a serum PSA level > 0.2 ng/ml and rising on 2 separate occasions at least 3 months after RP, and death.
Results: A total of 788 men (median age, 62; range: 32-83 years) were randomized. With a median follow-up of 5.1 years (range 0-11.2 years), no difference was seen in 3-year bPFS in men receiving neoadjuvant chemohormonal therapy and RP compared to RP alone (0.87 vs 0.82; p = 0.13; Figure). Expanding to the entire follow-up period, the bPFS rate was improved for the neoadjuvant arm (HR = 0.66; 95%CI: 0.47-0.94; Figure), however, the interpretation for the bPFS analyses was problematic due to 42% of patients not being evaluable for the primary endpoint because of receiving additional treatment prior to meeting the primary endpoint. An OS treatment evaluation provided evidence that patients randomized to neoadjuvant chemohormonal therapy and RP in this study had an improved OS rate relative to the RP-alone arm (HR = 0.67; 95% CI: 0.43-1.06).
Conclusions: Neoadjuvant ADT plus docetaxel followed by RP did not increase 3-year bPFS compared to RP alone in men with CLHRPC. There was evidence that over time, bPFS and OS were improved in the men receiving neoadjuvant chemohormonal therapy and RP versus the men receiving RP alone. However, the 42% non-evaluable rate for bPFS tempers enthusiasm for the bPFS endpoint results.
Source of Funding: U10CA180821, U10CA180882, U10CA180863 (CCTG), U10CA180888 (SWOG), and Sanofi-Aventis. ClinicalTrials.gov Identifier: NCT00430183.