Systematic Review and Network Meta-Analysis of Treatments for Chemotherapy-Naive Patients with Asymptomatic/Mildly Symptomatic Metastatic Castration-Resistant Prostate Cancer

Rachael McCool; Kelly Fleetwood; Julie Glanville; Mick Arber; Howard Goodall; Shevani Naidoo

doi:10.1016/j.jval.2018.03.012

Systematic Review and Network Meta-Analysis of Treatments for Chemotherapy-Naive Patients with Asymptomatic/Mildly Symptomatic Metastatic Castration-Resistant Prostate Cancer

Value Health. 2018 Oct;21(10):1259-1268. doi: 10.1016/j.jval.2018.03.012. Epub 2018 May 4.

Authors

Rachael McCool¹, Kelly Fleetwood², Julie Glanville³, Mick Arber³, Howard Goodall⁴, Shevani Naidoo⁵

Affiliations

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.

PMID: 30314628
DOI: 10.1016/j.jval.2018.03.012

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.

Keywords: enzalutamide; metastatic castration-resistant prostate cancer; network meta-analysis; systematic literature review.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
Asymptomatic Diseases / epidemiology
Asymptomatic Diseases / therapy*
Humans
Male
Prostatic Neoplasms, Castration-Resistant / diagnosis*
Prostatic Neoplasms, Castration-Resistant / drug therapy*
Prostatic Neoplasms, Castration-Resistant / epidemiology
Randomized Controlled Trials as Topic / methods
Treatment Outcome