For this study, eligible patients had cT1-T3, N0 prostate cancer with post radical prostatectomy ≥1 high risk factors defined as Gleason sum (GS) ≥8, pT3b, pT4, pN+, GS7 + positive margin or any of the following preoperative findings (in patients with neoadjuvant ADT): preoperative PSA >15 ng/ml, biopsy GS score >7, or PSA >10 ng/ml + biopsy GS >6. Subsequently, patients had to have a post-radical prostatectomy PSA ≤0.2 ng/mL and then were stratified by T-stage, N-stage, GS, and adjuvant radiation plan. Randomization was to Arm 1 – ADT (bicalutamide + goserelin for 2 years) or Arm 2 – ADT + 6 cycles of mitoxantrone 12 mg/m2 + prednisone 5 mg BID. The primary endpoint was overall survival (OS), and median OS was estimated to be 10 years in the ADT arm, requiring 680 patients/arm to detect a HR of 1.30 with 92% power and one-sided α of 0.05.
There were 983 patients, including 961 eligible patients intended to treat, with a median age of 60 years and median PSA 7.6 ng/mL who were randomized to Arm 1 (n=481) or Arm 2 (n=480) between 1999 and 2007. The trial’s DSMC subsequently recommended stopping accrual secondary to a higher leukemia rate in Arm 2 receiving mitoxantrone. Over a median follow-up of 11.2 years, the 10-year survival rate for Arm 1 was 87% and for Arm 2 86% (HR 1.06, 95%CI 0.79-1.43). The 10-year disease-free survival rate was also nonsignificant between the arms at 72% for each (HR 1.01, 95%CI 0.80-1.27). Importantly, there were significantly higher grade ≥3 adverse events in Arm 2 (56% vs 30%, p<0.001), as well as other cancer deaths (32% vs 15%, p=0.01).
In conclusion, this is an important study to highlight that systemic therapy benefits cannot be extrapolated from different disease stages and the importance of adequate follow-up in adjuvant prostate cancer trials. OS was higher than anticipated in both arms and MP did not improve OS, however it did increase other malignancy risk.
Clinical trial information: NCT00004124
Presented By: Maha Hussain, MD, Northwestern University Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
Co-Authors: Catherine M. Tangen, Ian Murchie Thompson, Gregory P. Swanson, David Peter Wood, Wael Sakr, Nancy Ann Dawson, Naomi B. Haas, Thomas W. Flaig, Tanya B. Dorff, Daniel W. Lin, E. David Crawford, David I. Quinn, Nicholas J. Vogelzang, L. Michael Glode
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA