Duration of Therapy For Oral Treatments
`in Patients With Metastatic Castration
`Resistant Prostate Cancer
`N. M. Engel-Nitz, PhD,1 A. S. Behl, PhD, MBA2, C. Blauer-Peterson, MPH1, N. A. Dawson, MD3
`1Optum, Eden Prairie, MN; 2Janssen Scientific Affairs, LLC, Horsham, MA: 3Georgetown University Hospital
`Background
`Results
`Patient Characteristics
`§ Abiraterone acetate (ABI) with prednisone and enzalutamide (ENZ) are oral
`treatments for patients with metastatic castration resistant prostate cancer
`§ Average age was 74 years (ENZ) and 73 years (ABI,P<0.05); Charlson
`(mCRPC).
`comorbidity scores were 6.4 (ENZ) and 5.9 (ABI), (P<0.001).
`Table 1. Patient Characteristics
`§ The literature suggests that the sequence in which these therapies are used
`may drive development of cross-resistance, potentially costing patients in
`terms of the effectiveness of subsequent treatments in the event of failure of
`the initial treatment.1
`§ However, there is little evidence on whether sequencing of therapy
`influences overall duration of therapy and subsequent outcomes, particularly
`progression to end-of-life care.
`Objective
`§ This study compared real-world duration of therapy and hospice use
`among patients initiated on ABI and ENZ.
`Methods
`Data Source and Study Design:
`§ Optum’s health claims database was used to conduct a retrospective study.
`The database includes commercial and Medicare Advantage enrollees with a
`national geographic distribution, with approximately 53 million unique
`individuals with medical and pharmacy coverage.
`Figure 1. Study Design
`
`ABI
`(N=1,095)
`Mean (Std. Dev)
`72.87 (9.32)
`5.92 (2.03)
`%
`17.63
`31.05
`39.27
`12.05
`%
`34.25
`65.75
`
`ENZ
`(N=421)
`Mean (Std. Dev)
`74.44 (9.46)
`6.35 (2.09)
`%
`18.29
`32.54
`38.48
`10.69
`%
`29.69
`70.31
`
`Characteristic
`
`Age (years)*
`Charlson Comorbidity Score**
`Region
`Northeast
`Midwest
`South
`West
`Insurance Type
`Commercial
`Medicare Advantage
`*P<0.05; **P<0.001
`Treatment Duration
`§ Average duration of treatment was 320 days (ABI) and 260 days (ENZ),
`P<0.001. Adjusted Cox proportional hazards analysis found a higher
`hazard of discontinuing treatment for ENZ vs. ABI (HR: 1.25; 95%
`confidence limits: 1.02, 1.52; P=0.032).
`Table 2. Treatment Patterns
`
`Measure
`
`Total days treated with ABI or ENZ**
`Duration of treatment: Time to ABI+ENZ
`treatment end (days)**
`Cox proportional hazards results, adjusted
`for demographics and clinical
`characteristics
`Discontinuation of treatment*
`
`*P<0.05; **P<0.001
`
`ABI
`(N=1,095)
`Mean (Std. Dev)
`293 (204)
`320 (220)
`
`ENZ
`(N=421)
`Mean (Std. Dev)
`240(166)
`260 (184)
`
`Hazard Ratio
`(ENZ vs. ABI
`reference)
`1.25
`
`[95% LCL, 95%
`UCL]
`
`[1.02, 1.52]
`
`Inclusion Criteria: Patients included in the study met the following criteria:
`§ Male patients (age 18+)
`§ Newly initiated on ABI or ENZ from 09/01/2012 to 06/30/2015;
`• Index date was identified as the date of first medication (ABI or ENZ)
`initiated.
`• Patients were excluded if they had claims for ABI or ENZ during 6-months
`prior to index date.
`§ ≥1 non-diagnostic claim with a prostate cancer diagnosis (ICD-9-CM 185.xx)
`from 6 months pre- through 30 days post-index date
`§ ≥6 pre-index and ≥3 months post-index health plan enrollment; patients were
`retained if follow-up shorter than 3 months was due to death.
`Variables
`§ Cohorts (ABI, ENZ) were based on the first medication initiated at index
`date.
`§ Duration of therapy with abiraterone acetate or enzalutamide was
`assessed as time from index date until the last date of all abiraterone
`acetate or enzalutamide treatment; this period includes treatment with other
`(switched) medications and gaps in therapy. In addition, total days treated
`were calculated as the sum of days supply from filled prescriptions for
`abiraterone acetate and enzalutamide.
`§ Hospice use was measured in medical claims based on procedures codes
`for hospice services and site of service codes; time from index date to first
`evidence of hospice, and time from hospice to death were measured.
`§ Mortality was assessed using the Social Security Master Death file, patient
`facility discharge status, and use of hospice services with subsequent health
`plan disenrollment.
`§ Enrollment data were used to identify age, insurance type, and geographic
`region of residence. Clinical characteristics were measured from medical
`and pharmacy claims, including Charlson Comorbidity Score2, bone/brain
`metastases, docetaxel, and pre- and post-index statin use.
`Analytic Methods
`§ Descriptive analyses compared ABI and ENZ on characteristics and
`outcomes; t-tests for means and chi-square tests for dichotomous variables.
`§ Cox proportional hazards compared ABI and ENZ on duration of therapy,
`with models adjusted for demographic and clinical characteristics.
`§ Time to hospice and time from entering hospice until death were evaluated.
`References
`
`1. Sartor O, Gillessen S. Treatment sequencing in metastatic castrate-resistant prostate cancer. Asian J Androl.
`2014 May-Jun; 16(3): 426–431.
`2. Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, Saunders LD, Beck CA, Feasby TE, Ghali
`WA, Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Medical Care.
`2005;43:1130-39.
`
`Figure 2. Discontinuation of Medication
`
`Hospice Use Patterns
`§ Hospice was used by 14.8% of ABI and 12.6% of ENZ cohort patients
`(P=0.270). Patients started hospice an average of 307 days (ABI) and
`234 days (ENZ) after initiating index treatment (P=0.024); patients died an
`average of 43 days (ABI) and 38 days (ENZ) after starting hospice
`(P=0.620).
`Figure 3. Time to Hospice and Death after starting Hospice
`
`ENZ
`
`ABI
`
`234
`
`38
`
`307
`
`Days to Hospice
`Days to Death
`43
`
`300
`
`350
`
`400
`
`150
`
`200
`
`250
`
`0
`50
`100
`Conclusions
`Patients with mCRPC who were initiated on ABI first were less likely to
`discontinue treatment, had longer time on treatment, and longer time to
`starting hospice compared with patients initiated on ENZ. These outcomes
`may serve as proxies for delayed progression or increased survival.
`Disclosure
`
`Funding for this study was provided to Optum by Janssen Scientific Affairs, LLC. Dr. Engel-Nitz
`and Ms. Blauer-Peterson are employees of Optum and stockholders of UnitedHealth Group.
`Dr. Behl is an employee and stockholder of Janssen Scientific Affairs, LLC. Dr. Dawson has
`consulted to Janssen.
`
`An electronic version of the poster can be viewed by scanning the QR code.
`The QR code is intended to provide scientific information for individual
`reference. The PDF should not be altered or reproduced in any way.
`
`Academy of Managed Care Pharmacy (AMCP) Nexus 2016, National Harbor, MD, USA; October 3-6, 2016
`
`JANSSEN EXHIBIT 2130
`Mylan v. Janssen IPR2016-01332
`
`