Clinical-Prostate cancer
Cost-effectiveness of abiraterone versus docetaxel in the treatment of metastatic hormone naïve prostate cancer

https://doi.org/10.1016/j.urolonc.2019.05.017Get rights and content

Highlights

  • Abiraterone and docetaxel increase PF-QALYs compared to ADT alone in mHNPC.

  • ICER for docetaxel versus ADT is $50,500/PF-QALY.

  • ICER for abiraterone versus docetaxel is $1,010,000/PF-QALY.

  • Docetaxel is more cost-effective than abiraterone in mHNPC treatment.

Abstract

Purpose

Prostate cancer is the second leading cause of cancer death in men in the US. Since 2015, landmark studies have demonstrated improved survival outcomes with the use of docetaxel (DCT) or abiraterone (AA) in addition to androgen deprivation therapy (ADT) in the metastatic hormone-naïve setting. These treatment strategies have not been prospectively compared but have similar overall survival benefits despite differing mechanisms of action, toxicity, and cost. We performed a cost-effectiveness analysis to provide insight into the value of AA vs. DCT in the first-line treatment of metastatic prostate cancer.

Materials and Methods

We developed Markov models by using a US-payer perspective and a 3-year time horizon to estimate costs (2018 US$) and progression-free quality-adjusted life years (PF-QALYs) for ADT alone, DCT, and AA. Health states were defined as initial state, treatment states according to experience of an adverse event, and progressed disease/death. State transition probabilities were derived from rates for drug discontinuation, frequency of adverse events, disease progression, and death from the randomized phase III trials ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) and LATITUDE. Univariate and probabilistic sensitivity analyses were conducted to evaluate model uncertainty.

Results

DCT resulted in an increase of 0.32 PF-QALYs and $16,100 in cost and AA resulted in an increase of 0.52 PF-QALYs and $215,800 in cost compared to ADT alone. The incremental cost-effectiveness ratio for DCT vs. ADT was $50,500/PF-QALY and for AA vs. DCT was $1,010,000/PF-QALY. Probabilistic sensitivity analysis demonstrated that at a willingness-to-pay threshold of $150,000/PF-QALY AA was highly unlikely to be cost-effective.

Conclusion

DCT is substantially more cost-effective than AA 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)

  • ND James et al.

    Abiraterone for prostate cancer not previously treated with hormone therapy

    NEJM

    (2017)
  • P Guyot et al.

    Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves

    BMC Med Res Methodol

    (2012)
  • AK Morgans et al.

    Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer

    J Clin Oncol

    (2018)
  • AM Bayoumi et al.

    Cost-effectiveness of androgen suppression therapies in advanced prostate cancer

    JNCI

    (2000)
  • T Younis et al.

    The cost–utility of adjuvant chemotherapy using docetaxel and cyclophosphamide compared with doxorubicin and cyclophosphamide in breast cancer

    Curr Oncol

    (2011)
  • L Zhong et al.

    Therapeutic options in docetaxel-refractory metastatic castration-resistant prostate cancer: a cost-effectiveness analysis

    PLOS ONE

    (2013)
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