Incidence of Second Primary Malignancies in Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the US

Xofigo (radium-223 dichloride) is an alpha-emitting pharmaceutical, which was approved for
the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone
metastases, and no known visceral metastatic disease. The long-term safety profile of Xofigo
is evaluated in the prospective REASSURE study, which estimates the incidence rates of second
primary malignancies in patients with CRPC receiving Xofigo.

To provide context on that, this retrospective study is conducted to estimate background
rates of second primary malignancies among patients with CRPC similar to those who are
treated with Xofigo.

Inclusion Criteria:

- Enrolled in both Medicare Parts A and B for at least 1 year before the cohort entry
date (minimum lookback period for comorbidities and treatments)

- Primary site code of prostate cancer (International Classification of Diseases for
Oncology, Third Edition [ICD-O-3] topography code C61.9) in SEER data

- Surgical castration or androgen deprivation therapy after prostate cancer diagnosis;
androgen deprivation therapy will be indicated by the use of any of the following
drugs: abarelix, bicalutamide, buserelin, cyproterone, degarelix, diethylstilbestrol,
estramustine, flutamide, gonadorelin, goserelin, histrelin, leuprolide,
medroxyprogesterone, megestrol, nafarelin, nilutamide, polyestradiol, triptorelin

- Evidence that prostate cancer was resistant to surgical castration or androgen
deprivation therapy ("castration-resistant prostate cancer"), as indicated by starting
one of the following second-line systemic therapies (cohort entry date): abiraterone,
cabazitaxel, docetaxel, enzalutamide, mitoxantrone, or sipuleucel-T

- Cohort entry date 01 January 2006 or later

- Age 65 years or older in the US on the cohort entry date

Exclusion Criteria:

- Enrollment in an HMO (Health Maintenance Organization) in the year before the cohort
entry date

- Diagnosis of any cancer other than prostate cancer or nonmelanoma skin cancer on or
before the cohort entry date

- Any diagnostic code for metastases other than bone metastases or lymph node metastases
on or before the cohort entry date

- Any claim for treatment with Xofigo on or before the cohort entry date.