1000 - Impact of Prior Local Therapy (LT) on Treatment Response and Survival of Men with Metastatic Castrate Resistant Prostate Cancer (mCRPC): A Pooled Analysis of COU-AA-302 and ACIS Trials

O. M. Azem¹, S. Roy², Y. Sun³, A. E. Cueto-Marquez⁴, R. Rauch⁵, K. Scharf⁶, L. A. DSouza⁷, C. J. D. Wallis⁸, F. Saad⁹, N. Camden⁴, S. C. Morgan¹⁰, S. Malone¹¹, O. Mohamad¹², D. E. Spratt¹³, and A. U. Kishan¹⁴; ¹Rush University Medical Center, Chicago, Illinois, OH, ²Rush University Medical Centre, Chicago, IL, ³Case Western Reserve University School of Medicine, Cleveland, OH, ⁴Rush University Medical Center, Chicago, IL, ⁵Rush Medical College, Chicago, IL, ⁶Air Club Centrum Podrozy Sp. z o.o., Warsaw, Poland, ⁷Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, ⁸Mount Sinai Hospital, UHN, University of Toronto, Toronto, ON, Canada, ⁹Département durologie, Centre Hospitalier de lUniversité de Montréal (CHUM), Montreal, QC, Canada, ¹⁰Division of Radiation Oncology, Department of Radiology, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada, ¹¹The Ottawa Hospital Cancer Center, Ottawa, ON, Canada, ¹²University of California San Francisco, San Francisco, CA, ¹³Case Western, Cleveland, OH, ¹⁴Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA

Purpose/Objective(s): Pre-clinical studies suggest that prior LT could portend neuroendocrine differentiation and could result in compromised response to subsequent lines of systemic therapy including androgen deprivation therapy (ADT) or androgen receptor pathway inhibitors (ARPI). In contrary, clinical studies show conflicting findings in this domain. Our analysis further explores whether prior local therapy plays a modifying role on the first line treatment effect on OS. Additionally, we investigate whether prior local therapy have an independent association with OS and radiographic progression free survival in this cohort. Materials/

Methods: We performed an individual patient data based meta-analysis of COU-AA-302 and ACIS trials that included men with chemotherapy naïve mCRPC. In the first trial, patients were randomly assigned to ADT versus ADT plus abiraterone (ADT+AA-P) while in the second one, patients were randomly assigned to ADT+AA-P versus ADT plus apalutamide plus AA-P (APA + AA-P). We applied a hierarchical multivariable Bayesian Cox proportional hazard regression model to determine if there was any difference in treatment effect on overall survival (OS) among patients stratified by prior LT. Further, we determined the independent association of exposure to prior LT with radiographic progression-free survival (rPFS) and OS in the entire study cohort.

Results: Overall, 2032 patients (n=527 in ADT group; n=1020 in ADT+AA-P group; n=485 to APA+AA-P) were included in this study; of whom, 339 in the ADT group, 559 in the AA-P group, and 234 in the APA+AA-P group had prior LT. Among patients with prior LT, 253 had radical prostatectomy (RP) alone, 345 had RP plus radiotherapy (RT), and 534 had RT alone, respectively. Relative to ADT+AA-P, we found no difference in treatment effect on OS from ADT alone (hazard ratio [HR] for the interaction term: 0.90; 95% credible interval [CrI]: 0.69-1.17) or APA+AA-P (HR for the interaction term: 1.29 [0.99-1.69]), among patients with and without prior LT. We did not find any significant association of LT modality with rPFS (HR for RP: 0.98 [0.81-1.18]; HR for RT: 0.99 [0.86-1.16]; and HR for RP+RT: 1.03 [0.86-1.23]) and OS (HR for RP: 0.84 [0.69-1.02]; HR for RT: 1.03 [0.89-1.19]; and HR for RP+RT: 0.88 [0.73-1.05]) in the overall study cohort.

Conclusion: In this meta-analysis, we did not find any significantly compromised treatment effects from first line ARPI in patients who received prior LT. Further, there was no significant association of prior LT modality with risk of radiographic progression or deaths, respectively.