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USE OF ABIRATERONE IN THE MANAGEMENT OF CASTRATION-RESISTANT
PROSTATE CANCER: A REAL-LIFE COST-EFFECTIVENESS STUDY
J. Rocha1, M. Vanhuyse2, A. G. Aprikian1, F. L. Cury3, W. Kassou1f, A. Dragomir1
1 Urology, 2 Medical Oncology, 3 Radiation Oncology,1-3 McGill University Health Centre
INTRODUCTION
Abiraterone impact on survival and costs of mCRPC management
Abi ± chemo
Pre-Abi
Abi post chemo
Pre-Abi
Survival Probability
Androgen ablation therapy (ADT) is the standard of care for metastatic,
recurrent or locally advance prostate cancer PCa[1]. It successfully reduces
tumor burden and can delay disease progression for several years [2].
However, virtually all patients will present disease progression to the castration
resistant (CR) stage. After PCa progression, second-line hormone therapy is
widely used, adding anti-androgens (AA) to continuous ADT [1]. Additionally,
since the majority of patients present metastases at the time of CRPC
diagnosis [3] with high prevalence of bone metastases [4], supportive therapy
with zoledronic acid, denosumab or palliative radiotherapy (pRxT) to reduce
bone-related morbidity and burden is often required [5,6].
Chemotherapy (chemo) with Docetaxel remained for most of the past decade
the only therapeutic option to metastatic (m) CRPC to offer a survival benefit
[7]. The introduction of Abiraterone, in 2012, change this panorama offering an
alternative for these patients and also for the ones not fit to receive chemo [8].
This study objectives were to estimate the real-life cost-effectiveness benefit of
the introduction of Abi treatment in the management of mCRPC post-docetaxel
in Quebec, Canada
Logrank p=0.0048
Logrank p=0.021
Months
Months
Hazard Ratio
Abi post chemo 0.65 (95% CI 0.44-0.96) p=0.03
Hazard Ratio
Abi ± chemo 0.82 (95% CI 0.64-1.05) p=0.12
STUDY COHORT
The study cohort was selected from the Régie de l’Assurance Maladie du
Québec (RAMQ) and Med-Echo databases, both of which administer public
healthcare insurance programs in Québec. It consisted of patients which have
shown evidence of CRPC and started chemo treatments from 2009-2010
(chemo only) defined as pre-Abi era, or Abi era for patients that received Abi
treatment from 2012-2013. Two groups were defined in Abi era: 1) Abi post
chemo group (for those that received Abi following chemo) and 2) Abi ±
chemo group (which include all patients that received Abi with or without
chemo).
METHODS
Patients’ demographics (age and residency - rural vs urban), residency
proximity to a treatment center (Radiation oncology (Rad. Onc.) or not),
diagnosed metastases, treatments received (Abi, chemo, AA, bone therapy are
presented as percentages, means (95%CI), or median (IQR) values as
applicable. Survival was evaluated by Kaplan-Meier and the difference in
survival between pre-Abi versus Abi post chemo or Abi ± chemo eras by logrank test. The association between Abi exposure and survival was evaluated
by Cox proportional hazards model adjusted for several co-variables. Cost was
estimated for primary mCRPC medications (Abiraterone, Chemo), medical
castration (LHRH), bone-target therapy (denosumab or zoleidronic acid). In
addition the costs of all other prescriptions during the study period (including
PCa related drugs as well as medications prescribed to other pathologies) was
determined. All costs were based on RAMQ costs and were reported in
Canadian dollars ($). The incremental cost-effectiveness ratio (ICER) was
obtained by dividing differences in costs and survival estimates in the Abi vs
pre-Abi periods. All tests were two-sided with a significance threshold of 5%.
Survival
Pre-Abi
Abi post chemo
Abi ± chemo
Abi
Mean
(95%
CI)
Chemo*
Median
(IQR)
Mean
(95%
CI)
Age
Mean
(95% CI)
Median (IQR)
Abi post chemo Abi ± chemo
(N= 303)
(n=80)
75.3
77.9
72.9
(74.4-76.1)
(77.0-78.8)
(71.0-74.8)
76.0
79.0
74.0
(71.0-79.0)
(73.0-84.0)
(67.0-80.0)
Abi ± chemo
(N= 303)
-
$19,196
$21,762
(16,538 – 21,853) (21,007- 23,517)
-
$17.,236
$20,194
(10,341 – 24,850) (10,341 – 27,585)
$5,034
(4,412 – 5,650)
$3,978
(3,452 – 4,489)
$3,947
(3,328-4,288)
Median
(IQR)
$4,644
(1,548 – 6,966)
$3,483
(2,322 – 5,418)
$3,096
(2,322-5,418)
Mean
(95%
CI)
$3,479
(3,080 – 3,878)
$3,614
(3,143 – 4,085)
$2,741
(2,488 – 2,994)
$2,933
(1,120 – 5,840
$3,480
(2,321 – 4,643)
$2,321
(1,159 – 4,426)
Medical
Castration
LHRH
Median
(IQR)
Bone-targeted
therapy
In our study the total number of prescriptions
filled during the study period was:
- Pre-Abi: 171
- Abi post chemo: 200
- Abi ± chemo: 178
In average drugs costs were:
For CRPC medications:
- Pre-Abi: $11,763
- Abi post chemo: $31,924
- Abi ± chemo: $31,660
For Other Medications:
- Pre-Abi: $5,264
- Abi post chemo: $5,520
- Abi ± chemo: $3,886
ICER = Δ cost / Δ effectiveness
Mean
(95%
CI)
Pre-Abi
(N=191)
Abi post chemo
(n=80)
Median
13 (IQR 11-14)
18 (IQR 14-21)
15 (IQR 14-19)
Primary
medication
RESULTS
Patient
demographics
and treatments
Pre-Abi
(N=191)
Treatment
costs
Mean
12.4 (±0.46)
15.9 (±0.7)
14.2 (±0.46)
Median
(IQR)
$3,028
(2,464 – 3,591)
$571
(0 – 6,177)
$5,084
(4,341 – 5,827)
$5,258
(2,729 – 7,273)
$3,309
(2,924- 3,693)
$2,908
(0 – 5,279)
ICER Abi post chemo: $71,070
ICER Abi ± chemo: $136,360
All medication
Mean
Cost of overall (95%
prescriptions CI)
$17,027
$37,475
$35,546
(15,047– 19,001) (33,452 – 41,489) (32,820 - 38,303)
Median
$15,184
$35,222
$32,220
(IQR)
(6,252 – 24,162) ( 23,590 – 50,031) (19,268 – 46,561)
Region – Rural
52 (27%)
13 (16%)
61 (20%)
Rad. Onc. Center
146 (76%)
56 (70%)
219 (72%)
Metastases
181 (95%)
76 (95%)
264 (87%)
CONCLUSIONS
Bone tx
112 (59%)
70 (87.5%)
226 (75%)
pRxT
104 (54%)
50 (62.5%)
149 (49%)
In our real-world cohort the introduction of Abi into the management of CRPC (since 2012) resulted in improved survival when
compared to the pre-Abi era. We found a 5 months median survival increment in the Abi post-chemo when compared to the preAbi period, which are similar with the Abi post docetaxel trial results (4.6 months). However, this increment is decreased to 3
months when Abi is prescribed to patients with or without prior chemotherapy, as it is in real-life clinical practice.
Treatment
duration
Primary
medication
Abi (months)
Mean
(95% CI)
AA (months)
-
6.4
(5.9-6.9)
-
5.0
(3.0-7.2)
5.9
(3.0-8.3)
Mean
(95% CI)
6.5
(5.7-7.3)
5.1
(4.5 - 5.8)
4.9
(4.3-5.5)
Median (IQR)
6
(2.0-9.0)
4.5
(3.0-7.0)
4.0
(3.0-7.0)
Acknowledgement
Mean
(95% CI)
48.6
(42.9-54.4)
52.1
(41.9-62.4)
60.1
(54.1-66.0)
This work was funded by Prostate Cancer Canada 2013 Discovery Grant. The Program in Health Economics of Prostate Cancer at the Urology
Division of McGill University is supported by the Cote-Sharp Family Foundation.
Median (IQR)
37.0
(21.0-64.5)
33.0
(21.0-76.0)
46.0
(21.0-90.0)
ADT
LHRH (months)
There is an important economic burden related to medication use over the CRPC period for all the groups studied. The PCa
associated costs account for half the costs in the pre-Abi group and the majority of medication costs in the Abi era. The addition of
Abi costs is responsible for 2/3 of all medication costs in the Abi groups.
5.63
(4.8-6.4)
Median (IQR)
Cycles Chemo
*Drug costs of chemo administered in hospitals were based on the Montreal
General Hospital pharmacy list and a body surface area of 1.9 m2.
Mean
(95% CI)
67.9
(62.0-73.9)
71.5
(74.6-76.5)
77.7
(71.6-83.9)
Median (IQR)
62
(41.0-89.0)
76.0
(72.0-80.0)
61.0
(34.0-114.0)
Chemo was received by all patients in the Pre-Abi and in the Abi post chemo
groups, while in the Abi ± chemo group only 33% of patients were exposed to
Chemo.
Finally, the ICER was $71K and $136K per life-year gained for each Abi post chemo and the Abi ± chemo groups, respectively,
when compared to pre-Abi era. Prescribing Abi to patients without prior chemo resulted in a reduced effectiveness, which led to a
increased ICER.
References
1. National Comprehensive Cancer Network, NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer. 2011.
2. Huggins, C. and C.V. Hodges, Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma
of the prostate. CA Cancer J Clin, 1972. 22(4): p. 232-40.
3. Kirby, M.,et al., Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract, 2011. 65(11): p. 1180-92.
4. Peters, J.L., et al., Bone loss associated with the use of LHRH agonists in prostate cancer. Prostate Cancer Prostatic Dis, 2001. 4(3): p. 161-166.
5.Fizazi, K., et al., Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study.
Lancet, 2011. 377(9768): p. 813-22.
6. Konski, A., Radiotherapy is a cost-effective palliative treatment for patients with bone metastasis from prostate cancer. Int J Radiat Oncol Biol Phys,2004. 60(5): p.1373-8.
7.Tannock, I.F., et al., Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med, 2004. 351(15): p. 1502-12.
8.Fizazi, K., et al., Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, doublePrinted by
blind, placebo-controlled phase 3 study. Lancet Oncol, 2012. 13(10): p. 983-92.