ASCO GU 2017: 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. - Session Highlights
The study was written back in 1999 when the definition of high risk prostate cancer population was being molded and several publication on the use of neoadjuvant and adjuvant ADT were being reported. The use of chemotherapy in patients with high risk post-prostatectomy features was also showing some promise with reports showing beneficial effect of estramustine in overall survival in patients undergoing both radical prostatectomy and radiation therapy. In addition, mitoxantrone + prednisone was also recently approved to the treatment on advance prostate cancer.
The premise of the trial was that the addition of mitoxantrone to ADT would improve both overall survival (OS) and progression free survival (PFS). The study was powered to detect a 30% increase in median survival with an expected accrual of 680 patients per arm. The eligibility criteria for the trial were patients with localized prostate cancer with one or more of the following pathological or clinical features: Gleason score ≥ 8, pT3b, pT4 or N1 disease, Gleason sum of 7 and a positive surgical margin, patients with a pre-operative PSA > 15 or a biopsy Gleason score of 7 or a serum PSA 10 and a biopsy score > 6. The patients were then stratified and randomized to ADT (bicalutamide plus Goserelin) for 24 months vs. ADT for 24 months plus 6 cycles of mitoxantrone plus prednisone.
The baseline patient characteristics for both groups were comparable with a median patient age of 60 years, with the great majority of patients being Caucasian (~80%), pre-prostatectomy PSA of was approximately 7.5, 17% of patients presented with N1 disease and the positive margin rate was approximately 60%. In regards to adverse events, 6 patients developed AML leukemia in the mitoxantrone group, the remainder of the adverse events was comparable in both groups. On survival analysis at median follow-up of approximately 11 years there was no difference seen in overall survival or progression free survival.
In conclusion, the trial demonstrates the feasibility of doing adjuvant trials in prostate cancer post radical prostatectomy. Survival was greater than anticipated in both arms of approximately 80% at 10 years. The addition of mitoxantrone increase the risk of developing AML leukemia and other cancers when added to ADT. More importantly, the addition of mitoxantrone does not improve prostate cancer survival or freedom of progression when added to 24 months of ADT in patients with high risk prostate cancer.
Dr. Slovin from Memorial Sloan Kettering Cancer Center presents a follow-up discussion of the above trial. Dr. Slovin focuses on the difficulty in accrual of patients for adjuvant prostate cancer trials due to the side effect profile of some the adjuvant therapy. She emphasizes on the lack of evidence that adjuvant therapy actually works in this patient population which could be related to the significant biological heterogeneity of prostate cancers assigned to his high risk group. She concludes by emphasizing the important of genetic markers, such as decipher, to help further stratify this high risk group of patients into categories and focus the adjuvant trials to those patients with highest risk of progression.
Presented By: L. Michael Glode, University of Colorado
Written By: Andres F. Correa, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA