Rachael McCool1, Kelly Fleetwood2, Julie Glanville3, Mick Arber3, Howard Goodall4, Shevani Naidoo5. 1. York Health Economics Consortium, University of York, York, UK. Electronic address: rachael.mccool@york.ac.uk. 2. Quantics, Edinburgh, UK. 3. York Health Economics Consortium, University of York, York, UK. 4. Jazz Pharmaceuticals, Oxford, UK. 5. Astellas Pharma, Inc., Chertsey, UK.
Abstract
OBJECTIVES: To estimate the relative effectiveness of enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer by conducting a systematic literature review and a network meta-analysis (NMA). METHODS: A systematic literature review identified randomized controlled trials comparing enzalutamide, abiraterone/prednisone, radium-223, sipuleucel-T, or docetaxel with each other or placebo in chemotherapy-naive or mixed populations (with and without prior chemotherapy) with asymptomatic/mildly symptomatic metastatic castration-resistant prostate cancer. Feasibility assessment evaluated the trials' suitability for NMA inclusion. The main outcomes were hazard ratios (HRs) for overall survival (OS) and radiographic progression-free survival (rPFS). RESULTS: Searches of relevant bibliographic databases, trial registers, Web sites, and conference abstracts conducted in October 2014 identified 25,712 records. Ten randomized controlled trials were eligible for the NMA. Enzalutamide was superior to placebo for OS and rPFS (fixed-effects model). NMA results (fixed-effects model) showed no evidence of a difference between enzalutamide and abiraterone/prednisone (HR 0.95 [95% CrI 0.77-1.16]), sipuleucel-T (HR 1.07 [95% CrI 0.84-1.37]), or radium-223 (HR 1.10 [95% CrI 0.87-1.37]) for OS. HRs were similar for the random-effects model. Nevertheless, results (fixed-effects model) suggested that enzalutamide was superior to abiraterone/prednisone (HR 0.59 [95% CrI 0.48-0.72]) and sipuleucel-T (HR 0.32 [95% CrI 0.25-0.42]) for rPFS. Results also suggested superiority of enzalutamide versus placebo, abiraterone/prednisone, or sipuleucel-T for time to chemotherapy. CONCLUSIONS: For rPFS, the NMA suggests that enzalutamide is superior to abiraterone/prednisone and sipuleucel-T. There is no evidence of a statistically significant difference in OS between enzalutamide and abiraterone/prednisone, sipuleucel-T, or radium-223. Given the limitations in network construction and underlying assumptions made to complete these analyses, results should be interpreted with caution.
OBJECTIVES: To estimate the relative effectiveness of enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer by conducting a systematic literature review and a network meta-analysis (NMA). METHODS: A systematic literature review identified randomized controlled trials comparing enzalutamide, abiraterone/prednisone, radium-223, sipuleucel-T, or docetaxel with each other or placebo in chemotherapy-naive or mixed populations (with and without prior chemotherapy) with asymptomatic/mildly symptomatic metastatic castration-resistant prostate cancer. Feasibility assessment evaluated the trials' suitability for NMA inclusion. The main outcomes were hazard ratios (HRs) for overall survival (OS) and radiographic progression-free survival (rPFS). RESULTS: Searches of relevant bibliographic databases, trial registers, Web sites, and conference abstracts conducted in October 2014 identified 25,712 records. Ten randomized controlled trials were eligible for the NMA. Enzalutamide was superior to placebo for OS and rPFS (fixed-effects model). NMA results (fixed-effects model) showed no evidence of a difference between enzalutamide and abiraterone/prednisone (HR 0.95 [95% CrI 0.77-1.16]), sipuleucel-T (HR 1.07 [95% CrI 0.84-1.37]), or radium-223 (HR 1.10 [95% CrI 0.87-1.37]) for OS. HRs were similar for the random-effects model. Nevertheless, results (fixed-effects model) suggested that enzalutamide was superior to abiraterone/prednisone (HR 0.59 [95% CrI 0.48-0.72]) and sipuleucel-T (HR 0.32 [95% CrI 0.25-0.42]) for rPFS. Results also suggested superiority of enzalutamide versus placebo, abiraterone/prednisone, or sipuleucel-T for time to chemotherapy. CONCLUSIONS: For rPFS, the NMA suggests that enzalutamide is superior to abiraterone/prednisone and sipuleucel-T. There is no evidence of a statistically significant difference in OS between enzalutamide and abiraterone/prednisone, sipuleucel-T, or radium-223. Given the limitations in network construction and underlying assumptions made to complete these analyses, results should be interpreted with caution.
Authors: Scott T Tagawa; Krishnan Ramaswamy; Ahong Huang; Jack Mardekian; Neil M Schultz; Li Wang; Rickard Sandin; Stanislav Lechpammer; Daniel J George Journal: Prostate Cancer Prostatic Dis Date: 2021-02-21 Impact factor: 5.455