237 - Local Therapy and Outcome in De Novo Metastatic Prostate Cancer: Individual Patient Data Analysis of the TITAN and ARASENS Trials
Presenter(s)
S. Roy1,2, A. U. Kishan3, M. Hussain4, N. Agarwal5, B. F. Tombal6, C. J. D. Wallis7, S. Chowdhury8, S. Malone9, U. Swami10, N. G. Zaorsky11, O. Mohamad12, S. C. Morgan13, Y. Sun14, R. R. Mckay15, E. Small16, A. Berlin17, H. Nagar18, A. Y. Jia19, F. Saad20, and D. E. Spratt11; 1Rush University Medical Centre, Chicago, IL, 2UH Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, 3Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, 4Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, 5Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 6Cliniques Universitaires Saint-Luc, Brussels, Belgium, 7Mount Sinai Hospital, UHN, University of Toronto, Toronto, ON, Canada, 8Guy's and St Thomas' NHS, London, United Kingdom, 9Division of Radiation Oncology, The Ottawa Hospital and the University of Ottawa, Ottawa, ON, Canada, 10Huntsman Cancer Institute, Salt Lake City, UT, 11Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, 12Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 13The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada, 14Case Western Reserve University School of Medicine, Cleveland, OH, 15University of California San Diego, La Jolla, CA, 16Department of Medicine, University of California San Francisco, San Francisco, CA, 17Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 18Memorial Sloan Kettering Cancer Center, New York, NY, 19Department of Radiation Oncology, University Hospitals Cleveland Medical Center/ Seidman Cancer Center, Cleveland, OH, 20Urology Department, University of Montreal Hospital Centre, Montreal, QC, Canada
Purpose/Objective(s):
While Local therapy confers superior outcomes in de novo metastatic prostate cancer (mPCa), preclinical studies have shown that local therapy could drive neuroendocrine differentiation which could portend resistance to systemic therapy including androgen deprivation therapy (ADT) with or without androgen receptor pathway inhibitors (ARPI). However, the clinical implications of these findings are unclear in de novo mPCa patients. We performed a pooled analysis of individual patient data (IPD) from 2 randomized controlled trials (RCTs) (TITAN and ARASENS) to determine the impact of local therapy on treatment response and overall survival (OS) in de novo mPCa.Materials/Methods:
In the ARASENS trial, patients with mPCa were randomly assigned to ADT plus docetaxel versus ADT plus docetaxel plus darolutamide. in the TITAN trial, patients were randomly assigned to ADT (+/-docetaxel) versus ADT plus apalutamide. Exposure to local therapy was defined as receipt of radical prostatectomy (RP) and/or radiotherapy (RT) after diagnosis of mPCa and prior to receipt of randomized treatment regimen. First, a multivariable Cox model with an interaction term was used to determine differential treatment effect from ARPI plus ADT among de novo mPCa patients stratified by exposure to local therapy after adjustment for confounders. Subsequently, we applied a multivariable Cox model to determine the independent association of local therapy with OS in the two treatment groups (ADT+/-docetaxel and ADT+/-docetaxel plus ARPI), respectively.Results:
Overall, 2201 patients were included in this study of whom 1853 patients presented with de novo mPCa. A total of 942 patients received ADT alone and 911 received ADT plus ARPI. Overall, 70 in the ADT group and 56 in the ADT plus ARPI group received local therapy – 30 received RP alone, 93 received RT alone, and 3 received RP plus RT, respectively. There was no evidence of differential treatment effect from ADT plus ARPI on OS across patients stratified by receipt of local therapy (p=0.70). There was evidence of superior OS with exposure to local therapy among patients randomly assigned to both ADT (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.47-1.00) and ADT plus ARPI group (HR 0.69; 95% CI 0.41-1.07), respectively. In the de novo M1 population, compared to no local therapy, RT was associated with superior OS (HR 0.70 [0.50-0.98]) while the study was not powered to determine any significant association of RP with OS (HR 0.73 [0.39-1.36]).Conclusion:
In this IPD analysis of two trials, exposure to local therapy in de novo mPCa was associated with evidence of superior OS in patients treated with either ADT or ADT plus ARPI, respectively. The findings emphasize the role of prostate directed local therapy even in ARPI treated men with de novo mPCa.