Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer |
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| Institution: | 1. Department of Cancer Medicine, Gustave Roussy Institute, Cancer Campus, Grand Paris, University of Paris-Sud, Villejuif, France;2. Institut Jean Godinot, Reims, France;1. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan;2. Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan;3. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan;4. Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital, Kanagawa, Japan;5. Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan;6. Department of Respiratory Internal Medicine, St. Marianna University School of Medicine, Yokohama-City Seibu Hospital, Kanagawa, Japan;7. Department of Respiratory Medicine, Fujisawa City Hospital, Kanagawa, Japan;8. Department of Biostatistics, Yokohama City University Medical Center, Kanagawa, Japan;9. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan;10. Thoracic Oncology Research Group, Kanagawa, Japan;11. Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan;12. Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan;1. Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan;2. Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan;1. Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;2. Janssen Research & Development, Los Angeles, CA, USA;3. Medical University of Vienna, Vienna, Austria;4. University of Montreal, Montreal, QC, Canada;5. University of Washington, Seattle, WA, USA;6. British Columbia Cancer Agency, Vancouver, BC, Canada;7. Janssen Research & Development, Raritan, NJ, USA;8. Institut Gustave Roussy, University of Paris Sud, Villejuif, France;1. Carolina Urologic Research Center, Myrtle Beach, SC, USA;2. King''s College London, and Guy''s, King''s and St Thomas'' Hospitals, London, UK;3. Department of Urology, Lille University, Lille, France;4. Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada;5. Centre for Applied Urological Research, Queen''s University, Kingston, ON, Canada;6. Astellas Pharma, Leiden, Netherlands;7. Astellas Pharma, Northbrook, IL, USA;8. Medivation, San Francisco, CA, USA;9. Department of Urology, Aachen University, Aachen, Germany;1. Department of Urology, Ghent University Hospital, Ghent, Belgium;2. Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium;3. Department of Medical Oncology, University Hospital Leuven, Leuven, Belgium;4. Department of Medical Oncology, AZ Turnhout, Turnhout, Belgium;5. Department of Medical Oncology, AZ Klina, Kalmthout, Belgium;6. Department of Medical Oncology, AZ Delta, Roeselare, Belgium;7. Department of Medical Oncology, Imelda Hospital, Bonheiden, Belgium;8. Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium;9. Department of Urology, Onze-Lieve-Vrouw Hospital, Aalst, Belgium;10. Department of Medical Oncology, Hopital De Jolimont, Haine Saint Paul, Belgium;11. Department of Medical Oncology, University Hospital Brussels, Jette, Belgium;12. Department of Medical Oncology, Institut Roi Albert II, Cliniques universitaires Saint Luc, Brussels, Belgium;13. Department of Medical Oncology, Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim, Antwerp, Belgium;14. Department of Medical Oncology, AZ Nikolaas, Sint-Niklaas, Belgium;15. Department of Medical Oncology, CHU Dinant-Godinne, Yvoir, Belgium;16. Department of Urology, AZ Groeninge, Kortrijk, Belgium;17. Department of Medical Oncology, ZNA Jan Palfijn, Merksem, Belgium;18. Department of Medical Oncology, AZ Jessa, Hasselt, Belgium;19. Department of Medical Oncology, St Luc Bouge, Namur, Belgium;20. Department of Medical Oncology, UZA/AZ Monica, Antwerp, Belgium;21. Department of Medical Oncology, Algemeen Stedelijk Ziekenhuis, Aalst, Belgium;22. Department of Medical Oncology, AZ Sint-Trudo, Sint-Truiden, Belgium;23. Department of Urology, AZ Sint-Andries, Tielt, Belgium;24. Department of Medical Oncology, Sainte-Elisabeth, Namur, Belgium |
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| Abstract: | BackgroundThere is an urgent need for qualified predictive biomarkers of sensitivity for the treatments used in patients with castration-resistant prostate cancer (CRPC). We attempted to identify ready-to-use clinical predictors of improved outcome in metastatic CRPC (mCRPC) patients treated with next generation androgen receptor (AR) axis targeted drugs.Patients and methodsWe reviewed a cohort of patients who received AR axis targeted drugs for CRPC at two major French cancer centres. The predictive role of several clinical, biological and radiological parameters on progression-free survival (PFS) was studied.ResultsThe study cohort consisted of 173 patients. Median duration of response to initial androgen deprivation therapy (ADT) (time to castration resistance, TTCRPC) was 17.8 months. The 50% prostate-specific antigen (PSA) response rate to AR axis targeted drugs was 16% (95% confidence interval (CI): 6–27) and 41% (95% CI: 30–47) in patients with TTCRPC of under and over 12 months respectively (p = 0.005). Median PFS was 2.8 months (95% CI: 2.1–3.9) and 5.8 (95% CI: 4.6–7.8; HR: 0.58, p = 0.002). In patients treated with post-docetaxel enzalutamide (n = 57), median PFS was 2.8 months and 8.6 months, (Hazard ratio (HR) = 3.1; 95% CI: 1.6–5.8, p = 0.0016) according to TTCRPC, whereas no difference was observed in placebo-treated patients (n = 27). The 50% PSA response rate to enzalutamide was 8% (95% CI: 0–38) and 58% (95% CI: 42–73) in patients with a TTCRPC of under and over 12 months respectively (p < 0.001).ConclusionThe previous duration of response to ADT is a predictor of sensitivity to next generation AR axis targeted drugs in patients with mCRPC. |
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| Keywords: | Prostate cancer Time to castration resistance Endocrine therapy Predictive factors Androgen receptor |
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