Fred Saad1, Johann de Bono2, Neal Shore3, Karim Fizazi4, Yohann Loriot4, Mohammad Hirmand5, Billy Franks6, Gabriel P Haas6, Howard I Scher7. 1. University of Montreal Hospital Centre, Montreal, QC, Canada. Electronic address: fred.saad@umontreal.ca. 2. Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK. 3. Carolina Urologic Research Center, Myrtle Beach, SC, USA. 4. Gustave Roussy, Cancer Campus Grand Paris, University of Paris Sud, Villejuif, France. 5. Medivation, Inc., San Francisco, CA, USA. 6. Astellas Global Medical Affairs, Inc., Northbrook, IL, USA. 7. Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Abstract
BACKGROUND:Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer (PCa) afterdocetaxel in the randomised, phase 3, double-blind, placebo-controlled, multinational Patients with Progressive Castration-Resistant Prostate Cancer Previously Treated withDocetaxel-Based Chemotherapy (AFFIRM) trial (NCT00974311). Prostate-specific antigen (PSA) is commonly used as a marker of PCa disease burden, and the relationship of baseline PSA level to consequent treatment effect is of clinical interest. OBJECTIVE: Exploratory analysis to evaluate any differences in patient characteristics and efficacy outcomes by baseline PSA level in the AFFIRM trial. DESIGN, SETTING, AND PARTICIPANTS: Post hoc subanalysis of all randomised patients (n=1199) from the AFFIRM trial. INTERVENTION: Participants were randomly assigned in a two-to-one ratio to receive oral enzalutamide 160 mg/d or placebo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The major clinical efficacy end points were overall survival (OS), radiographic progression-free survival (rPFS), and time to PSA progression (TTPP) versus placebo; baseline characteristics, treatment duration, and subsequent antineoplastic therapy were compared by baseline PSA quartile. RESULTS AND LIMITATIONS: Baseline PSA quartiles corresponded to the following PSA groups: <40 ng/ml (n=299), 40 to <111 ng/ml (n=300), 111 to <406 ng/ml (n=300), and ≥406 ng/ml (n=300). Enzalutamide consistently improved OS, rPFS, and TTPP compared with placebo across all subgroups, regardless of baseline PSA level. Hazard ratios for improvements in OS were 0.55 (95% confidence interval [CI], 0.36-0.85), 0.69 (95% CI, 0.47-1.02), 0.73 (95% CI, 0.53-1.01), and 0.53 (95% CI, 0.39-0.73) for PSA groups 1-4, respectively. The post hoc design of this analysis was not statistically powered to assess the relationship between baseline PSA and clinical efficacy outcomes. CONCLUSIONS: This post hoc analysis of the AFFIRM trial demonstrates consistent benefits in OS, rPFS, and TTPP with enzalutamide regardless of baseline disease severity, as assessed by PSA. PATIENT SUMMARY: Exploratory post hoc analysis of the AFFIRM trial showed that enzalutamide improves overall survival, radiographic progression-free survival, and time to prostate-specific antigen progression compared with placebo regardless of baseline disease severity, as assessed by prostate-specific antigen. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00974311.
RCT Entities:
BACKGROUND:Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer (PCa) after docetaxel in the randomised, phase 3, double-blind, placebo-controlled, multinational Patients with Progressive Castration-Resistant Prostate Cancer Previously Treated with Docetaxel-Based Chemotherapy (AFFIRM) trial (NCT00974311). Prostate-specific antigen (PSA) is commonly used as a marker of PCa disease burden, and the relationship of baseline PSA level to consequent treatment effect is of clinical interest. OBJECTIVE: Exploratory analysis to evaluate any differences in patient characteristics and efficacy outcomes by baseline PSA level in the AFFIRM trial. DESIGN, SETTING, AND PARTICIPANTS: Post hoc subanalysis of all randomised patients (n=1199) from the AFFIRM trial. INTERVENTION: Participants were randomly assigned in a two-to-one ratio to receive oral enzalutamide 160 mg/d or placebo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The major clinical efficacy end points were overall survival (OS), radiographic progression-free survival (rPFS), and time to PSA progression (TTPP) versus placebo; baseline characteristics, treatment duration, and subsequent antineoplastic therapy were compared by baseline PSA quartile. RESULTS AND LIMITATIONS: Baseline PSA quartiles corresponded to the following PSA groups: <40 ng/ml (n=299), 40 to <111 ng/ml (n=300), 111 to <406 ng/ml (n=300), and ≥406 ng/ml (n=300). Enzalutamide consistently improved OS, rPFS, and TTPP compared with placebo across all subgroups, regardless of baseline PSA level. Hazard ratios for improvements in OS were 0.55 (95% confidence interval [CI], 0.36-0.85), 0.69 (95% CI, 0.47-1.02), 0.73 (95% CI, 0.53-1.01), and 0.53 (95% CI, 0.39-0.73) for PSA groups 1-4, respectively. The post hoc design of this analysis was not statistically powered to assess the relationship between baseline PSA and clinical efficacy outcomes. CONCLUSIONS: This post hoc analysis of the AFFIRM trial demonstrates consistent benefits in OS, rPFS, and TTPP with enzalutamide regardless of baseline disease severity, as assessed by PSA. PATIENT SUMMARY: Exploratory post hoc analysis of the AFFIRM trial showed that enzalutamide improves overall survival, radiographic progression-free survival, and time to prostate-specific antigen progression compared with placebo regardless of baseline disease severity, as assessed by prostate-specific antigen. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00974311.
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: Neal D Shore; Matthew P Morrow; Trevor McMullan; Kimberly A Kraynyak; Albert Sylvester; Khamal Bhatt; Jocelyn Cheung; Jean D Boyer; Li Liu; Brian Sacchetta; Samantha Rosencranz; Elizabeth I Heath; Luke Nordquist; Heather H Cheng; Scott T Tagawa; Leonard J Appleman; Ronald Tutrone; Jorge A Garcia; Young E Whang; W Kevin Kelly; David B Weiner; Mark L Bagarazzi; Jeffrey M Skolnik Journal: Mol Ther Date: 2020-03-03 Impact factor: 11.454
Authors: Choung-Soo Kim; Ad Theeuwes; Dong Deuk Kwon; Young Deuk Choi; Byung Ha Chung; Hyun Moo Lee; Kang Hyun Lee; Sang Eun Lee Journal: Investig Clin Urol Date: 2016-05-10