Urologic Oncology: Seminars and Original Investigations
Clinical-Prostate cancerCost-effectiveness of abiraterone versus docetaxel in the treatment of metastatic hormone naïve prostate cancer
Introduction
Prostate cancer accounts for nearly 30,000 deaths annually in the US, and progressive metastatic disease carries significant morbidity [1]. Until 2015, the standard of care for frontline treatment of men with metastatic prostate cancer was androgen deprivation therapy (ADT) alone, either through surgical or chemical castration. Though initially effective for most patients, castration-resistance and clinical progression inevitably occurs at a median of approximately 1 year [2], [3]. In an analysis of men presenting with de novo metastatic prostate cancer between 1988 and 2009, no improvement in overall or disease-specific survival was found over time [4]. From 2010 to 2014, 6 new agents were Food and Drug Administration (FDA) approved for metastatic castration-resistant prostate cancer (mCRPC), but ADT alone remained the preferred first line therapy for metastatic hormone-naïve prostate cancer (mHNPC).
However, since 2015, 3 landmark studies have established a role for 2 agents that were initially approved for castration-resistant disease for use in the initial metastatic hormone-naïve setting. The ECOG-ACRIN 3805 ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) and STAMPEDE studies treated patients with 6 cycles of docetaxel (DCT) at the time of ADT initiation prior to the development of castration resistance, and demonstrated an improvement in time to progression as well as overall survival (OS) [5], [6]. Shortly thereafter, the LATITUDE and STAMPEDE studies demonstrated that the addition of abiraterone (AA) acetate plus prednisone therapy concomitantly with ADT improved progression-free survival (PFS) and OS [7], [8].
While the STAMPEDE study had a more heterogeneous population as it included patients with nonmetastatic disease, the CHAARTED and LATITUDE study populations were very similar, particularly when comparing the high-volume cohort from CHAARTED with the entire cohort from LATITUDE. The reported hazard ratios for OS compared with ADT alone (with similar median follow-up times of approximately 30 months) were strikingly similar at 0.62 for AA and 0.60 for DCT. These dramatic improvements have led to the FDA approval of both drugs for mHNPC and NCCN category 1 recommendations for their use. However, these treatment approaches are vastly different in their mechanisms of action, modes of delivery, toxicity profiles, and costs.
We conducted a comparative effectiveness study of the 2 treatment strategies vs. ADT alone based on the CHAARTED and LATITUDE trials, as there is no prospective head-to-head comparison of AA vs. DCT in this setting to help guide treatment decisions. We created a Markov model to estimate treatment effects and costs to provide insight into the value of these different therapies in first-line treatment of mHNPC over the first 3 years from the time of diagnosis.
Section snippets
Model Structure
We used a Markov Cohort model to estimate direct costs, progression-free quality adjusted life years (PF-QALYs), and incremental cost effectiveness ratios (ICERs) for the 3 treatment strategies of AA, DCT, and ADT in patients with mHNPC from a US payer perspective. State transitions probabilities were defined according to the model structure (Fig. 1), probabilities of adverse events, and survival time data. Each model cycle represented 3 weeks, corresponding to the length of a DCT treatment
Results
In the base case, over a 3-year time horizon, adding DCT to ADT resulted in an increase of 0.32 PF-QALYs and $16,100 in cost, and adding AA to ADT resulted in an increase of 0.52 PF-QALYs and $215,800 in cost. This results in an ICER for DCT vs. ADT of $50,500/PF-QALY, and an ICER of AA vs. DCT of $1,010,000/PF-QALY. One-way sensitivity analyses demonstrated that the model was most sensitive to changes in survival probabilities for each agent (Fig. 2—Tornado diagrams). Results were also
Discussion
We performed a cost-effectiveness analysis of AA plus ADT and DCT plus ADT in the treatment of hormone naïve metastatic prostate cancer. While both strategies provided incremental benefit compared to ADT alone, the incremental cost per PF-QALY was substantially higher for AA than DCT. This is despite the model being intentionally structured to favor AA, in that it does not ascribe additional side effects to AA compared to ADT alone and generously discounts utility values associated with a
References (33)
- et al.
Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial
Lancet Oncol
(2013) - et al.
Survival with newly diagnosed metastatic prostate cancer in the "Docetaxel Era": data from 917 patients in the control arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019)
Eur Urol
(2015) - et al.
Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial
Lancet
(2016) - et al.
Markov models for health economic evaluation modelling in R with the heemod package
Value in Health
(2016) - et al.
Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial
Lancet Oncol
(2018) - et al.
Cost-effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the united states
Clin Therap
(2009) - et al.
Increasing incidence of metastatic prostate cancer in the United States (2004-2013)
Prostate Cancer Prostatic Dis
(2016) - et al.
No improvement noted in overall or cause-specific survival for men presenting with metastatic prostate cancer over a 20-year period
Cancer
(2014) - et al.
Chemohormonal therapy in metastatic hormone-sensitive prostate cancer
NEJM
(2015) - et al.
Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer
NEJM
(2017)
Abiraterone for prostate cancer not previously treated with hormone therapy
NEJM
Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves
BMC Med Res Methodol
Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer
J Clin Oncol
Cost-effectiveness of androgen suppression therapies in advanced prostate cancer
JNCI
The cost–utility of adjuvant chemotherapy using docetaxel and cyclophosphamide compared with doxorubicin and cyclophosphamide in breast cancer
Curr Oncol
Therapeutic options in docetaxel-refractory metastatic castration-resistant prostate cancer: a cost-effectiveness analysis
PLOS ONE
Cited by (27)
Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review of Economic Evaluations
2022, Clinical Genitourinary CancerCitation Excerpt :At the WTP threshold of 30 to 50 000.0€/LY or QALY, the strategy of ADT + docetaxel appears to be the most cost-effective relative to innovative treatments (ie, ADT + AA, ADT + enzalutamide, or ADT + apalutamide) for the first-line treatment of patients with mHSPC. Only a price reduction of AA, enzalutamide, or apalutamide will change this conclusion, as shown by the EEs conducted by Chiang et al, Aguiar et al, Hird et al, Ramamurthy et al, and Sung et al.22,25,27,29,33 This price reduction will be related to the introduction of the generic versions of AA, enzalutamide, and apalutamide into the European market in the near future, which is expected to be associated with a price reduction of 70%. With the exception of ADT + docetaxel or ADT alone (reference treatment because it is the historical treatment), the most cost-effective innovative treatment appears to be ADT + AA.
Cost-Effectiveness of Systemic Treatments for Metastatic Castration-Sensitive Prostate Cancer: An Economic Evaluation Based on Network Meta-Analysis
2022, Value in HealthCitation Excerpt :In Europe, a similar price disparity is expected in 2022 when abiraterone acetate’s regulatory exclusivity expires.13 Moreover, although previous work examined the cost-effectiveness of certain treatments for mCSPC,14,15 to the best of our knowledge, none compared the cost-effectiveness of the current market basket of treatments. Thus, we examined the cost-effectiveness of systemic treatments for mCSPC from a US healthcare sector perspective over a lifetime horizon.
Cost-effectiveness Analysis of Innovative Therapy for Patients with Newly Diagnosed Hormone-Sensitive Metastatic Prostate Cancer
2021, Clinical Genitourinary CancerCitation Excerpt :The results of our CEA suggest that docetaxel for patient with mHSPC is cost-effective in comparison with AA. This result is consistent with the literature.24-28 Strategies SA1DOCE→ABI and SA2DOCE→ENZA are dominant for cohort A, whereas SB2DOCE→DOCE and SB1DOCE→CABA are dominant for cohort B.
Advanced Prostate Cancer: Treatment Advances and Future Directions
2020, Trends in CancerAdvancements in health economic evaluation research of drug treatment regimens for prostate cancer
2023, Chinese Journal of Cancer Prevention and Treatment
- 1
Co-first authors.