Skeletal-Related Events after Abiraterone or Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer: A Population-Based Study Using the SEER-Medicare Linked Dataset - Beyond the Abstract
Our objective was to evaluate whether there is a differential risk of SREs in men treated with either abiraterone or enzalutamide on a population level. We conducted a retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER)-Medicare Linked Database. Key eligibility criteria were men with prostate cancer aged ≥65 years at first abiraterone or enzalutamide prescription (index date) from 2011-2015. The primary outcome was a composite endpoint of SRE (pathologic fracture, spinal cord compression, or surgery or radiation to bone) after the index date. We created multivariable logistic regression models including key demographic and clinical covariates with death as a competing risk.
We identified a cohort of 5,856 patients, of whom 4,207 (72%) received abiraterone and 1,649 (28%) received enzalutamide. Eight-hundred and thirty-seven (14.3%) patients had ≥1 SRE after index date. In multivariable analyses, there was no difference in SRE risk based on abiraterone and enzalutamide (HR=0.99 for enzalutamide, 95% CI 0.84-1.16, P=0.890). This may be due to their similar efficacy in the systemic treatment of prostate cancer, which likely translates to similar control of bone metastases. In the absence of a significant difference in SRE risk, decision-making between abiraterone and enzalutamide should be informed by prior therapies, comorbidities, toxicity profiles, and patient preferences.
We also found that denosumab was associated with lower SRE risk (HR=0.75, 95% CI 0.64-0.88, P=0.001). This finding contributes to accumulating evidence that the SRE-preventative benefits of bone-modifying agents in mCRPC likely translate to real-world populations of men with mCRPC receiving abiraterone or enzalutamide. A number of other factors were found to be associated with an increased risk of SREs, including Northeast SEER region and earlier abiraterone or enzalutamide prescription year. Older age and Alzheimer's disease were associated with a decreased risk of SREs.
Our study is limited by the retrospective design, potential imprecision with SRE and mCRPC identification, absence of data on definite drug exposure duration, and absence other known SRE risk/protective factors in the database.
Our large population-based study suggests that there is no difference in risk of SRE between abiraterone and enzalutamide. Decision-making between the two therapies should be informed by prior therapies, comorbidities, toxicity profiles, and patient preferences. Denosumab has evidence of benefit in SRE prevention in a real-world population of men with mCRPC starting abiraterone or enzalutamide.
Written by: Daniel Kwon, MD, Assistant Clinical Professor, Hospital-Based Oncology & Genitourinary Medical Oncology, University of California, San Francisco
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