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Abstract
Objectives
To quantify the association between dose reductions of abiraterone acetate plus prednisone (AAP) or enzalutamide and prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC). Changes in medication-taking patterns of AAP or enzalutamide may arise due to clinical (e.g. toxicity) and non-clinical (e.g. patient compliance) reasons in men with mCRPC. However, it is unclear how this affects PSA progression.
Methods
Veterans Health Administration electronic health record database was used to identify Veterans diagnosed with prostate cancer who initiated AAP or enzalutamide (index) from April 2010 to December 2016. PSA progression was defined as the first rise in PSA of ≥2 ng/mL and ≥25% above nadir. The relative dose intensity (RDI) was defined as the ratio of the total dispensed dose over the last two months to the standard recommended dose and was updated monthly. Dose reduction was assessed using a threshold of RDI < 80%.
Results
The cohort included 6069 Veterans aged 74.6 years on average. Mean follow-up was 12.3 months. PSA progression occurred in 62.7% of patients. About 63.6% of AAP- and 67.2% of enzalutamide-treated patients had ≥1 occurrence of RDI <80%. RDI <80% was associated with an 8.8% higher risk of PSA progression (hazard ratio [HR] = 1.088; p = .019; 95% confidence interval [CI] [1.014; 1.166]).
Conclusions
Dose reduction was observed in most patients and was associated with significantly higher risk of PSA progression in men with mCRPC. These results suggest future efforts to minimize dose reductions for non-clinical reasons are warranted and that patient adherence should be encouraged to limit the risk of PSA progression.
Transparency
Declaration of funding
This work was supported by Janssen Scientific Affairs, LLC. The sponsor was involved in all aspects of the research, including the study design; the collection, analysis, and interpretation of data; writing of the report; and the decision to submit the article for publication.
Declaration of financial and other relationships
DP, RHB, SN, and PL are employees of Analysis Group Inc., a consulting company that has received research grants from Janssen Scientific Affairs, LLC to conduct this study. SL was an employee of Janssen Scientific Affairs when this work was conducted. SJF is a consultant for Janssen Scientific Affairs, LLC. A peer reviewer on this manuscript has been a speaker or advisor for Astellas, Astra Zeneca, Bayer, MSD, Janssen, Pfizer, and Sanofi. The peer reviewers have no other relevant financial relationships or otherwise to disclose.
Acknowledgements
Medical writing assistance was provided by Samuel Rochette, an employee of Analysis Group, Inc., which provided paid consultancy services to Janssen Scientific Affairs, LLC. for the conduct of this study. The authors would like to thank Mu Cheng from Analysis Group, Inc. for analytical support, and Alexander Fuld, MD, from White River Junction VA Medical Center and Dartmouth Geisel School of Medicine for clinical support and guidance.
Data availability statement
The data that support the findings of this study are available from VHA, but restrictions apply to the availability of these data and so are not publicly available.