BACKGROUND: There 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 METHODS: We 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. RESULTS: The 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). CONCLUSION: The previous duration of response to ADT is a predictor of sensitivity to next generation AR axis targeted drugs in patients with mCRPC.
BACKGROUND: There 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 METHODS: We 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. RESULTS: The 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). CONCLUSION: The previous duration of response to ADT is a predictor of sensitivity to next generation AR axis targeted drugs in patients with mCRPC.
Authors: R R McKay; L Werner; M Fiorillo; M Nakabayashi; P W Kantoff; M-E Taplin Journal: Prostate Cancer Prostatic Dis Date: 2016-08-09 Impact factor: 5.554
Authors: Anuradha Jayaram; Anna Wingate; Daniel Wetterskog; Vincenza Conteduca; Daniel Khalaf; Mansour Taghavi Azar Sharabiani; Fabio Calabrò; Lorraine Barwell; Susan Feyerabend; Enrique Grande; Alberto Martinez-Carrasco; Albert Font; Alfredo Berruti; Cora N Sternberg; Rob Jones; Florence Lefresne; Marjolein Lahaye; Shibu Thomas; Shilpy Joshi; Dong Shen; Deborah Ricci; Michael Gormley; Axel S Merseburger; Bertrand Tombal; Matti Annala; Kim N Chi; Ugo De Giorgi; Enrique Gonzalez-Billalabeitia; Alexander W Wyatt; Gerhardt Attard Journal: JCO Precis Oncol Date: 2019-09-24
Authors: Joaquim Bellmunt; Thian Kheoh; Margaret K Yu; Matthew R Smith; Eric J Small; Peter F A Mulders; Karim Fizazi; Dana E Rathkopf; Fred Saad; Howard I Scher; Mary-Ellen Taplin; Ian D Davis; Dirk Schrijvers; Andrew Protheroe; Arturo Molina; Peter De Porre; Thomas W Griffin; Johann S de Bono; Charles J Ryan; Stéphane Oudard Journal: Eur Urol Date: 2015-10-24 Impact factor: 20.096