178809-197

Adjuvant androgen deprivation (ADT) versus mitoxantrone plus prednisone (MP) plus ADT in high-risk prostate cancer (PCa) patients following radical prostatectomy: A phase III intergroup trial (SWOG S9921) NCT00004124.

Category: 
Genitourinary Cancer
Session Type and Session Title: 
Oral Abstract Session A: Prostate Cancer
Poster Session A: Prostate Cancer
Abstract Number: 

02

Poster Board Number: 
Poster Session A Board #A3
Citation: 
J Clin Oncol 35, 2017 (suppl 6S; abstract 2)
Author(s): 
L. Michael Glode, Catherine M. Tangen, Maha Hussain, 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, Ian Murchie Thompson; University of Colorado Denver, Aurora, CO; Fred Hutchinson Cancer Research Center, Seattle, WA; Northwestern University, Chicago, IL; The University of Texas Health Science Center at San Antonio, San Antonio, TX; Beaumont Physician Partners and Clinical Faculty, Royal Oak, MI; Wayne State University School of Medicine, Detroit, MI; Lombardi Comprehensive Cancer Center, Washington, DC; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; University of Colorado Cancer Center, Aurora, CO; Keck School of Medicine, University of Southern California, Los Angeles, CA; University of Washington, Seattle, WA; University of Colorado, Aurora, CO; University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA; Comprehensive Cancer Centers of Nevada, Las Vegas, NV

Abstract Disclosures

Abstract: 

Background: High risk localized Pca patients are more likely to relapse and suffer morbidity/mortality from metastatic disease after prostatectomy. Adjuvant ADT can reduce this risk. We hypothesized that MP in addition to two years of ADT could further reduce mortality from PCa. Methods: Participants with clinically localized (T1-T3, N0, M0) PCa received radical prostatectomy. Eligibility required ≥ 1 high risk criteria defined as Gleason sum ≥8; pT3b or pT4 or N1; Gleason 7 with positive margin; any one of these preoperative findings: PSA>15ng/ml, biopsy Gleason >7, biopsy Gleason >6 with PSA>10. ADT arm consisted of bicalutamide and goserelin for 2 years. ADT+MP arm received ADT plus 6 cycles of M 12mg/m2+ P 5mg BID. Primary endpoint was survival (OS). Median OS was anticipated to be 10 years in ADT arm requiring 680 patients/arm to detect a hazard ratio of 1.30 with 92% power and one-sided α=0.05. Results: S9921 enrolled patients from 10/99 to 1/07 when the DSMC recommended stopping due to increased incidence of leukemia in the ADT+MP arm. Of 983 patients randomized, 22 ineligible. 481 eligible on ADT and 480 on ADT+MP. Patients were stratified by stage (≤pT2, ≥pT3, N0 or N+), Gleason score, and intent to receive adjuvant radiation (RT) (Y/N). Median age was 60 years, 84% were white, presurgical PSA was 7.6 ng/ml, 16% had positive nodes, 26% intended to receive RT, 63% had positive margins. 11 ADT and 20 ADT+ MP received no protocol treatment. Median follow-up is 11.2 years. Conclusions: Survival was greater than anticipated in both arms. MP increases the risk of leukemia. There is no evidence that MP improves PCa specific survival when added to 2 years of adjuvant ADT. Clinical trial information: NCT00004124

Endpoint# of Events
ADT/ADT+MP
10-year estimate
ADT/ADT+MP
HR ADT+MP vs. ADT
(95% CI), p-value**
Overall survival84/8987%/86%1.05 (0.78, 1.42), p=0.74
Recurrence-free survival149/14784%/84%0.98 (0.78, 1.23), p=0.83
Deaths
    PCa14/12
    Other cause58/57
    Unknown12/20
P-value
Grade 3 or Higher Adverse Event30%/56%P <0.0001
Leukemia 2nd primary0/6P=0.015#

** adjusted for stratification factors, HR = hazard ratio, # 2-sided Fisher’s exact test