Dataset Information

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness.

ABSTRACT:

Background

Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources.

Objective

To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting.

Design, setting, and participants

We modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy.

Intervention

SOC was hormone therapy for ?2 yr and radiotherapy in some patients. Docetaxel (75mg/m²) was administered alongside SOC for six three-weekly cycles.

Outcome measurements and statistical analysis

The model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs).

Results and limitations

The model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled.

Conclusions

Docetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available.

Patient summary

Starting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.

SUBMITTER: Woods BS

PROVIDER: S-EPMC6692495 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness.

Woods Beth S BS Sideris Eleftherios E Sydes Matthew R MR Gannon Melissa R MR Parmar Mahesh K B MKB Alzouebi Mymoona M Attard Gerhardt G Birtle Alison J AJ Brock Susannah S Cathomas Richard R Chakraborti Prabir R PR Cook Audrey A Cross William R WR Dearnaley David P DP Gale Joanna J Gibbs Stephanie S Graham John D JD Hughes Robert R Jones Rob J RJ Laing Robert R Mason Malcolm D MD Matheson David D McLaren Duncan B DB Millman Robin R O'Sullivan Joe M JM Parikh Omi O Parker Christopher C CC Peedell Clive C Protheroe Andrew A Ritchie Alastair W S AWS Robinson Angus A Russell J Martin JM Simms Matthew S MS Srihari Narayanan N NN Srinivasan Rajaguru R Staffurth John N JN Sundar Santhanam S Thalmann George N GN Tolan Shaun S Tran Anna T H ATH Tsang David D Wagstaff John J James Nicholas D ND Sculpher Mark J MJ

European urology oncology 20180914 6

<h4>Background</h4>Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources.<h4>Objective</h4>To assess whether adm ...[more]

PMID: 31158087

Similar Datasets

Project description:BackgroundSTAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.MethodsWe randomly allocated patients in 2?:?1 ratio to standard-of-care (SOC; control group) or SOC?+?docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.ResultsBetween 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n?=?724) or SOC?+?docetaxel (n?=?362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2?months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR?=?0.81, 95% CI 0.69-0.95, P?=?0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P?=?0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR?=?0.66, 95% CI 0.57-0.76, P?<?0.001) and progression-free survival (HR?=?0.69, 95% CI 0.59-0.81, P?<?0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P?>?0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1?year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1?year without prior progression).ConclusionsThe clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

Project description:BACKGROUND:Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS:Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC?+?ZA), standard of care plus docetaxel (SOC?+?Doc), or standard of care with both zoledronic acid and docetaxel (SOC?+?ZA?+?Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided ? for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS:2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC?+?ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC?+?Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC?+?ZA?+?Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC?+?ZA, 288 (52%) receiving SOC?+?Doc, and 269 (52%) receiving SOC?+?ZA?+?Doc. INTERPRETATION:Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING:Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Project description:Background:Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC?+?AAP versus SOC?+?DocP. Method:Recruitment to SOC?+?DocP and SOC?+?AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for??2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC?+?docetaxel 75?mg/m2 3-weekly×6?+?prednisolone 10?mg daily; or SOC?+?abiraterone acetate 1000?mg?+?prednisolone 5?mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC?+?AAP, and HR?>?1 favours SOC?+?DocP. Results:A total of 566 consenting patients were contemporaneously randomised: 189 SOC?+?DocP and 377 SOC?+?AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66?years and median PSA 56?ng/ml. With median follow-up 4?years, 149 deaths were reported. For overall survival, HR?=?1.16 (95% CI 0.82-1.65); failure-free survival HR?=?0.51 (95% CI 0.39-0.67); progression-free survival HR?=?0.65 (95% CI 0.48-0.88); metastasis-free survival HR?=?0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR?=?1.02 (0.70-1.49); and symptomatic skeletal events HR?=?0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting??1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC?+?DocP, and 40%, 7% and 1% SOC?+?AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions:This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration:Clinicaltrials.gov: NCT00268476.

Project description:Adding abiraterone acetate (AA) plus prednisolone (P) to standard of care (SOC) improves survival in newly diagnosed advanced prostate cancer (PC) patients starting hormone therapy. Our objective was to determine the value for money to the English National Health Service (NHS) of adding AAP to SOC. We used a decision analytic model to evaluate cost-effectiveness of providing AAP in the English NHS. Between 2011-2014, the STAMPEDE trial recruited 1917 men with high-risk localised, locally advanced, recurrent or metastatic PC starting first-line androgen-deprivation therapy (ADT), and they were randomised to receive SOC plus AAP, or SOC alone. Lifetime costs and quality-adjusted life-years (QALYs) were estimated using STAMPEDE trial data supplemented with literature data where necessary, adjusting for baseline patient and disease characteristics. British National Formulary (BNF) prices (£98/day) were applied for AAP. Costs and outcomes were discounted at 3.5%/year. AAP was not cost-effective. The incremental cost-effectiveness ratio (ICER) was £149,748/QALY gained in the non-metastatic (M0) subgroup, with 2.4% probability of being cost-effective at NICE's £30,000/QALY threshold; and the metastatic (M1) subgroup had an ICER of £47,503/QALY gained, with 12.0% probability of being cost-effective. Scenario analysis suggested AAP could be cost-effective in M1 patients if priced below £62/day, or below £28/day in the M0 subgroup. AAP could dominate SOC in the M0 subgroup with price below £11/day. AAP is effective for non-metastatic and metastatic disease but is not cost-effective when using the BNF price. AAP currently only has UK approval for use in a subset of M1 patients. The actual price currently paid by the English NHS for abiraterone acetate is unknown. Broadening AAP's indication and having a daily cost below the thresholds described above is recommended, given AAP improves survival in both subgroups and its cost-saving potential in M0 subgroup.

Dataset Information

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness.

Background

Objective

Design, setting, and participants

Intervention

Outcome measurements and statistical analysis

Results and limitations

Conclusions

Patient summary

Publications

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets