Dataset Information

Cost-effectiveness analysis of cabazitaxel for metastatic castration resistant prostate cancer after docetaxel and androgen-signaling-targeted inhibitor resistance.

ABSTRACT:

Background

The aim of our study was to evaluate the cost-effectiveness of cabazitaxel versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel who had progression within 12?months while receiving an alternative inhibitor (abiraterone or enzalutamide) from a US payer's perspective.

Methods

To conduct the cost-effectiveness analysis, a Markov decision model was established. Three health states (progression-free survival (PFS), progressive disease (PD) and death) were included, and the incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint. The willingness-to-pay (WTP) threshold was set at $100,000.00/quality-adjusted life year (QALY), and discounted rates were set at 3% annually. Efficacy data were derived from the CARD trial and Weibull distribution curves were modeled to fit the survival curves. The robustness of the analysis was tested with a series of one-way sensitivity analyses and probabilistic sensitivity analyses.

Results

Overall, the incremental effectiveness and cost of cabazitaxel versus androgen-signaling-targeted inhibitors (ASTIs) were 0.16 QALYs and $49,487.03, respectively, which yielded an ICER of $309,293.94/QALY. Our model was mostly sensitive to the duration of PFS in the cabazitaxel group, cost of cabazitaxel and utility of the PFS state. At a WTP threshold of $100,000.00/QALY, cabazitaxel was the dominant strategy in 0% of the simulations.

Conclusions

Cabazitaxel is unlikely to be a cost-effective treatment option compared with ASTIs in patients with mCRPC previously treated with docetaxel who had progression within 12?months while receiving ASTIs.

SUBMITTER: Zhang PF

PROVIDER: S-EPMC7791718 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cost-effectiveness analysis of cabazitaxel for metastatic castration resistant prostate cancer after docetaxel and androgen-signaling-targeted inhibitor resistance.

Zhang Peng-Fei PF Xie Dan D Li Qiu Q

BMC cancer 20210107 1

<h4>Background</h4>The aim of our study was to evaluate the cost-effectiveness of cabazitaxel versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel who had progression within 12 months while receiving an alternative inhibitor (abiraterone or enzalutamide) from a US payer's perspective.<h4>Methods</h4>To conduct the cost-effectiveness analysis, a Markov decision model was established. Three health states (prog ...[more]

PMID: 33413230

Similar Datasets

Project description:Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples. We evaluated associations between plasma AR and overall/progression-free survival (OS/PFS) and prostate-specific antigen (PSA) response rate in 163 docetaxel-treated patients. OS was significantly shorter in case of AR gain (hazard ratio [HR]=1.61, 95% confidence interval [CI]=1.08-2.39, p=0.018), but not PFS (HR=1.04, 95% CI 0.74-1.46, p=0.8) or PSA response (odds ratio=1.14, 95% CI=0.65-1.99, p=0.7). We investigated the interaction between plasma AR and treatment type after incorporating updated data from our prior study of 73 chemotherapy-naïve, abiraterone/enzalutamide-treated patients, with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC patients receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR=0.16, 95% CI=0.06-0.46, p<0.001) and PFS (HR=0.31, 95% CI=0.12-0.80, p=0.02). Specifically, we reported a significant difference for OS favoring abiraterone/enzalutamide for AR-normal patients (HR=1.93, 95% CI=1.19-3.12, p=0.008) and a suggestion favoring docetaxel for AR-gained patients (HR=0.53, 95% CI=0.24-1.16, p=0.11). These data suggest that AR-normal patients should receive abiraterone/enzalutamide and AR-gained could benefit from docetaxel. This treatment selection merits prospective evaluation in a randomized trial. PATIENT SUMMARY: We investigated whether plasma androgen receptor (AR) predicted outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel, and we performed an exploratory analysis in patients treated with docetaxel or AR-directed drugs as first-line mCRPC therapy. We showed that plasma AR normal favored hormonal treatment, whilst plasma AR-gained patients may have had a longer response to docetaxel, suggesting that plasma AR status could be a useful treatment selection biomarker.

Project description:BACKGROUND:Multiple androgens drive prostate cancer progression and higher pre-treatment levels of androgens, even within the castrate range, have been previously shown to be associated with an improved overall survival (OS) in mCRPC. Docetaxel impairs microtubules, has androgen receptor (AR) inhibitory effects and is used in both the castration resistant and sensitive settings, where androgen dynamics may impact outcome. The present analysis evaluates the association of decline in serum androgen levels (Testosterone (T), Androstenedione (A) and DHEA in docetaxel-treated mCRPC patients with OS. METHODS:Data from 1050 men treated on CALGB 90401 with docetaxel, prednisone and either bevacizumab or placebo were evaluated. Eligibility required progressive mCRPC and no prior chemotherapy. Pre-treatment, 6 week and progression serum assays for T, A and DHEA were performed via tandem Liquid Chromatography-Mass Spectrometry (LC-MS/MS). Changes in T, A and DHEA levels from baseline to 6 weeks were calculated as the ratio of 6-week over baseline. The proportional hazards model was used to assess the prognostic significance of changes in T, A, and DHEA from baseline to 6 weeks in predicting OS adjusting for known prognostic factors. RESULTS:Median baseline values for T, A, and, DHEA were 1.0, 13.5, and 8.1?ng/dL respectively while 6 week levels were 0.64, 7.0, and 6.8?ng/dL respectively. Median OS for low testosterone decline is 20.9 months vs 26.3 months for high testosterone decline. In multivariable analysis including known prognostic variables, change in testosterone levels was independently associated with greater OS; the hazard ratio for death with each unit increase in the 6-week/baseline ratio is 1.02 (95% CI?=?1.01-1.03, p?=?0.001). Decline in A and DHEA were not significant predictors of OS. In multivariable analysis change in the serum changes did not predict PFS however the ratio of T at 6-weeks over baseline was prognostic of ?50% decline in PSA with an odds ratio of 0.93 (95% CI?=?0.85-0.98, p-value?=?0.039). CONCLUSIONS:Declines in testosterone during docetaxel treatment is associated with a longer survival, consistent with a favorable prognostic significance of higher serum androgens in the CRPC.

Project description:BackgroundCabazitaxel significantly improves clinical outcomes compared with a second androgen receptor-targeted agent (ARTA) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and an ARTA (abiraterone or enzalutamide), as demonstrated in the CARD trial (NCT02485691). We aimed to estimate healthcare costs avoided with the use of cabazitaxel as a third-line (3 L) treatment versus a second ARTA from a US payer perspective.MethodsModel inputs were based on the CARD trial, published sources, and estimates of typical clinical care patterns by genitourinary oncologists (n = 3). Assessed time points were 6, 12, 18, and 24 months. Outcomes included progression-free survival (PFS), radiographic PFS (rPFS), and overall survival (OS); hospitalization and intensive care unit (ICU) days; and costs (reported in 2020 US dollar [USD] and converted into Euro) to manage symptomatic skeletal events (SSEs), adverse events (AEs), and end-of-life care.ResultsAt 18 months, in a cohort of 100 patients, the use of cabazitaxel was estimated to result in 9 more patients achieving rPFS, 2 more patients achieving PFS, and 17 more survivors versus a second ARTA. The costs of SSEs, AEs, and end-of-life care were $498,909 (€424,073), $276,198 (€234,768), and $808,785 (€687,468), respectively, for cabazitaxel and $627,569 (€533,434), $251,124 (€213,455), and $1,028,294 (€874,050), respectively, for a second ARTA. Cabazitaxel was estimated to be associated with a 21% reduction in both SSE management and end-of-life care costs. Hospitalization cost was $1,442,870 (€1,226,440) for cabazitaxel and $1,728,394 (€1,469,135) for a second ARTA, representing an estimated 17% reduction in these costs. Cabazitaxel, as compared with a second ARTA, was associated with 58 fewer hospitalization days and 2 fewer ICU days and was estimated to avoid $323,095 (€274,630, 17%) in total costs, driven by SSEs management and end-of-life care.ConclusionThe use of cabazitaxel as a 3 L treatment after docetaxel and an ARTA in patients with mCRPC is estimated to result in clinical benefits (longer rPFS, PFS, and OS) and lower healthcare resource utilization (fewer hospitalization and ICU days), compared with a second ARTA.

Project description:Purpose: The effectiveness of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib for metastatic castration-resistant prostate cancer (MCRPC) with multiple loss-of-function alterations in genes that are involved in DNA repair has been demonstrated. We aimed to evaluate the cost-effectiveness of genomic test-directed olaparib on MCRPC from the US payer perspective. Methods: A partitioned survival model was adopted to project the disease course of MCRPC had at least one gene alteration in BRCA1, BRCA2 and ATM (Scenario A) and has alterations in any of all 15 prespecified genes (Scenario B) after next-generation sequencing test. The efficacy and toxicity data were gathered from the PROfound trial. Clinical probabilities related to survival were estimated from the reported survival probabilities in each PROfound group. Cost and health preference data were derived from the literature. The incremental cost-effectiveness ratio (ICER) was measured. Subgroup analysis and sensitivity analysis were performed for exploring the model uncertainties. Results: Olaparib yielded an additional 0.063 and 0.068 of quality-adjusted life year (QALY) with the augmented cost of $7,382 and saved the cost of $ 1,980 compared to standard care in scenario A and B, respectively, which yielded an ICER of $116,903/QALY and a cost-saving option. The lower weekly cost related to olaparib treatment led to the dominant findings in scenario B. The varied results between scenario A and B could be partly explained by different the number need to screen for identifying eligible patients who could be administered with olaparib, which sharply augmented the costs of the olaparib arm in scenario A. Subgroup analysis and sensitivity analysis revealed the results were generally robust in both of two scenarios. Conclusion: The genomic test-directed olaparib is a preferred option compared with standard care strategy for men with MCRPC who had any of all 15 prespecified genes.

Dataset Information

Cost-effectiveness analysis of cabazitaxel for metastatic castration resistant prostate cancer after docetaxel and androgen-signaling-targeted inhibitor resistance.

Background

Methods

Results

Conclusions

Publications

Cost-effectiveness analysis of cabazitaxel for metastatic castration resistant prostate cancer after docetaxel and androgen-signaling-targeted inhibitor resistance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets