250 - The Role of Docetaxel in Addition to Salvage Radiation and Androgen Deprivation in Men with High-Risk Prostate Cancer Post-Prostatectomy: Results of NRG GU002
Presenter(s)
M. D. Hurwitz1, T. Johnson2, A. O. Sartor3, W. K. Kelly4, C. T. Lee5, Y. Xiao6, R. T. Dess7, J. M. Michalski8, S. S. Mao9, T. Gunter10, A. P. Dicker11, M. V. Mishra12, T. G. Scroggins Jr13, A. Parthasarathy14, T. L. Bott-Kothari15, A. Balogh16, S. Pugh17, P. L. Nguyen18, and H. M. Sandler19; 1Department of Radiation Medicine, New York Medical College, Valhalla, NY, 2American College of Radiology, Philadelphia, PA, 3Tulane Cancer Center, New Orleans, LA, 4Thomas Jefferson University, Philadelphia, PA, 5Ohio State University Comprehensive Center, Columbus, OH, 6Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 7Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 8Washington University School of Medicine, St. Louis, MO, 9Allegheny Health Network Cancer Institute at Allegheny General Hospital, Pittsburgh, PA, United States, 10University of Oklahoma Health Sciences Center, Oklahoma City, OK, 11Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, 12Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 13Ochsner Health System, New Orleans, LA, United States, 14Rohnert Park Cancer Center, Rohnert Park, CA, United States, 15University of Michigan, Ann Arbor, MI, 16Tom Baker Cancer Centre, Calgary, AB, Canada, 17NRG Oncology Statistics and Data Management Center, Philadelphia, PA, 18Mass General Brigham Cancer Institute, Boston, MA, 19Oregon Health and Science University, Portland, OR
Purpose/Objective(s):
The role of chemotherapy in management of high-risk patients (pts) post-prostatectomy (RP) remains to be defined. NRG/RTOG 0621 was a single arm study in which subjects received post-RP radiation (RT), androgen deprivation therapy (ADT) and 6 cycles of docetaxel (CT) after completion of RT. 3 yr FFP was 73% vs. 50% in a pre-defined historical control group. A very high-risk group was identified whose PSA failed to nadir to =0.2ng/ml after RP. NRG GU002 is a follow-on randomized phase II/III study that hypothesized addition of CT to RT and ADT in men whose PSA failed to nadir to =0.2ng/ml post-RP would improve freedom from progression (FFP; phase II) and subsequently metastasis free survival (MFS; phase III). The role of Decipher genomic classification (GC), to select pts likely to benefit from CT was a key secondary objective.Materials/Methods:
Pts received a median dose of 6840cGy with 6 mo of ADT +/- 6 cycles of CT (75mg/m2). For the phase II primary endpoint of FFP, 89 events from 297 pts had 80% power to detect a hazard ratio (HR) = 0.7 with a 1-sided type I error = 20%. Between arm differences were tested with a stratified one-sided log rank test. Adjusted HRs and confidence intervals (CIs) were calculated using Cox models. Key secondary endpoints were overall survival (OS), local-regional failure (LRF), proportion of pts with undetectable PSA with non-castrate testosterone at 2.5 years, and to assess the impact of GC.Results:
The phase II portion closed due to slow accrual with 175 subjects enrolled and 165 randomized between 12/2016 and 9/2022. Median f/u was 5.3 yrs. Pt and tumor characteristics were evenly matched between groups. 78% of pts were GC high risk. 5-year FFP was 48.9% (95% CI: 37.3-60.4) in the RT + ADT arm vs. 62.6% (95% CI: 51.4-73.9) in the RT + ADT + CT arm (HR=0.67, 60% CI: 0.55-0.83, stratified one-sided log rank p=0.092). Interaction between tx arm and GC category was significant (p=0.013). RT + ADT + CT was superior in the Low/Int Risk group (2 events out of 19) compared to RT + ADT (10 events out of 18) (HR=0.13, 60% CI: 0.07-0.24). There was no between arm difference in the High-Risk group (HR=0.98, 60% CI: 0.78-1.23). There was no difference in OS with 8 deaths, 4 in each arm. There was a significant difference in favor of RT + ADT + CT for LRF (HR=0.33, 95% CI: 0.15-0.73, p=0.0064). The proportion of patients with undetectable PSA with non-castrate testosterone at 2.5 years was similar between the RT + ADT and RT + ADT + CT arms. Toxicity was higher in the CT arm, mainly due to grade 3-4 febrile neutropenia (12% vs. 0%), fatigue (8.4% vs. 0%), decreased lymphocytes (18.1% vs. 2.4%), neutrophils (16.8% vs. 0%), and decreased WBCs (10.8% vs. 0%).Conclusion:
For patients whose PSAs fail to nadir to =0.2ng/ml post RP, the addition of CT to RT and ADT appears to improve FFP. Interaction between treatment arm and GC category was significant in favor of CT in the Low/Int risk group. Further randomized studies of use of CT and GC in high-risk post-RP pts are warranted.