Patient time and out-of-pocket costs for long-term prostate cancer survivors in Ontario, Canada.

PURPOSE: Time and out-of-pocket (OOP) costs can represent a substantial burden for cancer patients but have not been described for long-term cancer survivors. We estimated these costs, their predictors, and their relationship to financial income, among a cohort of long-term prostate cancer (PC) survivors. METHODS: A population-based, community-dwelling, geographically diverse sample of long-term (2-13 years) PC survivors in Ontario, Canada, was identified from the Ontario Cancer Registry and contacted through their referring physicians. We obtained data on demographics, health care resource use, and OOP costs through mailed questionnaires and conducted chart reviews to obtain clinical data. We compared mean annual time and OOP costs (2006 Canadian dollars) across clinical and sociodemographic characteristics and examined the association between costs and four groups of predictors (patient, disease, system, symptom) using two-part regression models. RESULTS: Patients' (N = 585) mean age was 73 years; 77 % were retired, and 42 % reported total annual incomes less than $40,000. Overall, mean time costs were $838/year and mean OOP costs were $200/year. Although generally low, total costs represented approximately 10 % of income for lower income patients. No demographic variables were associated with costs. Radical prostatectomy, younger age, poor urinary function, current androgen deprivation therapy, and recent diagnosis were significantly associated with increased likelihood of incurring any costs, but only urinary function significantly affected total amount. CONCLUSIONS: Time and OOP costs are modest for most long-term PC survivors but can represent a substantial burden for lower income patients. Even several years after diagnosis, PC-specific treatments and treatment-related dysfunction are associated with increased costs. IMPLICATIONS FOR CANCER SURVIVORS: Time and out-of-pocket costs are generally manageable for long-term PC survivors but can be a significant burden mainly for lower income patients. The effects of PC-specific, treatment-related dysfunctions on quality of life can also represent sources of expense for patients.

The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis.

The impact of the Oncotype Dx (ODX) breast cancer assay on adjuvant chemotherapy (ACT) treatment decisions has been evaluated in many previous studies. However, it can be difficult to interpret the collective findings, which were conducted in diverse settings with limited sample sizes. We conducted a systematic review and meta-analysis to synthesize the results and provide insights about ODX utility. Studies, identified from PubMed, Embase, ASCO, and SABCS, were included if patients had ER+, node -, early-stage breast cancer, reported use of ODX to inform actual ACT decisions. Information was summarized and pooled according to: (1) distribution of ODX recurrence scores (RS), (2) impact of ODX on ACT recommendations, (3) impact of ODX on ACT use, and (4) proportion of patients following the treatment suggested by the ODX RS. A total of 23 studies met inclusion criteria. The distribution of RS categories was 48.8 % low, 39.0 % intermediate, and 12.2 % high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4 % of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT were: 28.2 % overall, 5.8 % low, 37.4 % intermediate, and 83.4 % high. Low RS patients were significantly more likely to follow the treatment suggested by ODX versus high RS patients RR: 1.07 (1.01­1.14) [corrected].The pooled results are consistent with most individual studies to date. The increased proportion of intermediate scores relative to original estimates may have implications for the clinical utility and cost impacts of testing. In addition, low versus high RS patients were significantly more likely to follow the ODX results, suggesting a tendency toward less aggressive treatment, despite a high ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use versus standard approaches, suggesting that additional studies are warranted.

Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial.

Early hormone-receptor-positive breast cancer is a chronic relapsing disease that can remain clinically silent for many years. The NCIC-CTG MA.17/BIG 1-97 trial randomized disease-free early breast cancer patients who had received five years of adjuvant tamoxifen to either letrozole or placebo and was the first to demonstrate a benefit with extended endocrine therapy. MA.17/BIG 1-97 was stopped at the first interim analysis because disease free survival was strongly prolonged in the letrozole arm. Subsequent subset analyses and longer follow up have shown that this therapy improved survival across all groups, particularly among women with node-positive disease and those that were pre-menopausal at time of study enrolment. The MA.17/BIG 1-97 study should be considered a paradigm for extended adjuvant endocrine therapy in hormone-receptor-positive early breast cancer.

Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases.

BACKGROUND: Bone metastases are common in patients with hormone-refractory prostate cancer. In a study of autopsies of patients with prostate cancer, 65%-75% had bone metastases. Bone metastases place a substantial economic burden on payers with estimated total annual costs of $1.9 billion in the United States. Skeletal-related events (SREs), including pathologic fractures, spinal cord compression, surgery to bone, and radiation to bone, affect approximately 50% of patients with bone metastases. They are associated with a decreased quality of life and increased health care costs. Zoledronic acid is an effective treatment in preventing SREs in solid tumors and multiple myeloma. Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. A Phase 3 clinical trial (NCT00321620) demonstrated that denosumab had superior efficacy in delaying first and subsequent SREs compared with zoledronic acid. However, the economic value of denosumab has not been assessed in patients with hormone-refractory prostate cancer. OBJECTIVE: To compare the cost-effectiveness of denosumab with zoledronic acid in the treatment of bone metastases in men with hormone-refractory prostate cancer. METHODS: An Excel-based Markov model was developed to assess costs and effectiveness associated with the 2 treatments over a 1- and 3-year time horizon. Because the evaluation was conducted from the perspective of a U.S. third-party payer, only direct costs were included. Consistent with the primary outcome in the Phase 3 trial, effectiveness was assessed based on the number of SREs. The model consisted of 9 health states defined by SRE occurrence, SRE history, disease progression, and death. A hypothetical cohort of patients with hormone-refractory prostate cancer received either denosumab 120 mg or zoledronic acid 4 mg at the model entry and transitioned among the 9 health states at the beginning of each 13-week cycle. Transition probabilities associated with experiencing the first SRE, subsequent SREs, disease progression, and death were primarily derived from the results of the Phase 3 clinical trial and were supplemented with published literature. The model assumed that a maximum of 1 SRE could occur in each cycle. Drug costs included wholesale acquisition cost, health care professional costs associated with drug administration, and drug monitoring costs, if applicable. Nondrug costs included incremental costs associated with disease progression, costs associated with SREs, and terminal care costs, which were derived from the literature. Adverse event (AE) costs were estimated based on the incidence rates reported in the Phase 3 trial. Resource utilization associated with AEs was estimated based on consultation with a senior medical director employed by the study sponsor. All costs were presented in 2010 dollars. The base case estimated the incremental total cost per SRE avoided over a 1-year time horizon. Results for a 3-year time horizon were also estimated. One-way sensitivity analyses and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the model. RESULTS: In the base case, the total per patient costs incurred over 1 year were estimated at $35,341 ($19,230 drug costs and $16,111 nondrug costs) for denosumab and $27,528 ($10,960 drug costs and $16,569 nondrug costs) for zoledronic acid, with an incremental total direct cost of $7,813 for denosumab. The estimated numbers of SREs per patient during the 1-year period were 0.49 for denosumab and 0.60 for zoledronic acid, resulting in an incremental number of SREs of -0.11 in the denosumab arm. The estimated incremental total direct costs per SRE avoided with the use of denosumab instead of zoledronic acid were $71,027 for 1 year and $51,319 for 3 years. The 1-way sensitivity analysis indicated that the results were sensitive to the drug costs, median time to first SRE, and increased risk of SRE associated with disease progression. Results of the PSA showed that based on willingness-to-pay thresholds of $70,000, $50,000, and $30,000 per SRE avoided, respectively, denosumab was cost-effective compared with zoledronic acid in 49.5%, 17.5%, and 0.3% of the cases at 1 year, respectively, and 79.0%, 49.8%, and 4.1% of the cases at 3 years, respectively. CONCLUSIONS: Although denosumab has demonstrated benefits over zoledronic acid in preventing or delaying SREs in a Phase 3 trial, it may be a costly alternative to zoledronic acid from a U.S. payer perspective.

Reduction in physician reimbursement and use of hormone therapy in prostate cancer.

BACKGROUND: Use of androgen suppression therapy (AST) in prostate cancer increased more than threefold from 1991 to 1999. The 2003 Medicare Modernization Act reduced reimbursements for AST by 64% between 2004 and 2005, but the effect of this large reduction on use of AST is unknown. METHODS: A cohort of 72,818 men diagnosed with prostate cancer in 1992-2005 was identified from the Surveillance, Epidemiology, and End Results database. From Medicare claims data, indicated AST was defined as 3 months or more of AST in the first year in men with metastatic disease (n = 8030). Non-indicated AST was defined as AST given without other therapies such as radical prostatectomy or radiation in men with low-risk disease (n = 64,788). The unadjusted annual proportion of men receiving AST was plotted against the median Medicare AST reimbursement. A multivariable model was used to estimate the odds of AST use in men with low-risk and metastatic disease, with the predictor of interest being the calendar year of the payment change. Covariates in the model included age in 5-year categories, clinical tumor stage (T1-T4), World Health Organization grade (1-3, unknown), Charlson comorbidity (0, 1, 2, ≥ 3), race, education, income, and tumor registry site, all as categorical variables. The models included variations in the definition of AST use (≥ 1, ≥ 3, and ≥ 6 months of AST). All statistical tests were two-sided. RESULTS: AST use in the low-risk group peaked at 10.2% in 2003, then declined to 7.1% in 2004 and 6.1% in 2005. After adjusting for tumor and demographic covariates, the odds of receiving non-indicated primary AST decreased statistically significantly in 2004 (odds ratio [OR] = 0.70, 95% confidence interval = 0.61 to 0.80) and 2005 (OR = 0.61, 95% confidence interval = 0.53 to 0.71) compared with 2003. AST use in the metastatic disease group was stable at 60% during the payment change, and the adjusted odds ratio of receiving AST in this group was unchanged in 2004-2005. CONCLUSIONS: In this example of hormone therapy for prostate cancer, decreased physician reimbursement was associated with a reduction in overtreatment without a reduction in needed services.

Healthcare costs in postmenopausal women with hormone-positive metastatic breast cancer.

OBJECTIVES: This study examines costs for postmenopausal women with hormone receptor positive (HR+) metastatic breast cancer (mBC). METHODS: Data were obtained from the IHCIS National Managed Care Benchmark Database from 1/1/2001 to 6/30/2006. Women aged 55-63 years were selected for the study if they met the inclusion criteria, including diagnoses for breast cancer and metastases, and at least two fills for a hormone medication. Patients were followed from the onset of metastases until the earliest date of disenrollment from the health plan or 6/30/2006. Patient characteristics were examined at time of initial diagnoses of metastases, while costs were examined post-diagnosis of metastases and prior to receipt of chemotherapy (pre-chemotherapy initiation period) and from the date of initial receipt of chemotherapy until end of data collection (post-chemotherapy initiation period). Costs were adjusted to account for censoring of the data. RESULTS: The study population consisted of 1,266 women; mean (SD) age was 59.05 (2.57) years. Pre-chemotherapy initiation, unadjusted inpatient, outpatient, and drug costs were $4,392, $47,731, and $5,511, while these costs were $4,590, $57,820, and $38,936 per year, respectively, post-chemotherapy initiation. After adjusting for censoring of data, total medical costs were estimated to be $55,555 and $70,587 in the first 12 months and 18 months, respectively in the pre-chemotherapy initiation period. Post-chemotherapy initiation period, 12-month and 18-month adjusted total medical costs were estimated to be $87,638 and $130,738. LIMITATIONS: The use of an administrative claims database necessitates a reliance upon diagnostic codes, age restrictions, and medication use, rather than formal assessments to identify patients with post-hormonal women with breast cancer. Furthermore, such populations of insured patients may not be generalizable to the population as a whole. CONCLUSIONS: These findings suggest that healthcare resource use and costs - especially in the outpatient setting - are high among women with HR+ metastatic breast cancer.

Cost utility analysis of early adjuvant letrozole or anastrozole versus tamoxifen in postmenopausal women with early invasive breast cancer: the UK perspective.

Five years with the aromatase inhibitors letrozole or anastrozole is clinically superior to 5 years tamoxifen in postmenopausal women with early breast cancer. This paper analyses the cost-effectiveness of the aromatase inhibitors compared to tamoxifen using the same health economic model. A Markov model describes lifetime incidence of breast cancer events and treatment-related adverse events. Probabilities of disease progression, adverse events, and utility values were estimated using secondary sources; costs of breast-cancer care were obtained from a primary costing study. The incremental cost per QALY gained of letrozole vs. tamoxifen is 10,379pounds (95% CI 6,705-23,574pounds), and of anastrozole versus tamoxifen is 11,428pounds (95% CI 6,211-48,795pounds). If a 5-year carry over effect for the reduction in breast cancer events is assumed, the incremental costs per QALY gained compared to tamoxifen are 6,253pounds (95% CI 3,675-14,766pounds) for letrozole and 7,015pounds (95% CI 3,316-31,997pounds) for anastrozole. Five years of letrozole or anastrozole therapy is cost-effective in postmenopausal women with early breast cancer. Though the respective confidence intervals show significant overlap, letrozole has a 95% probability of being more cost-effective than tamoxifen at a 20,000pounds QALY value, whilst anastrozole has an 85% probability.

Comparative economic analysis of aromatase inhibitors and tamoxifen in the treatment of hormone-dependent breast cancer.

Within the past 2 years three separate groups reported marked improvements in relapse-free survival when trastuzumab was added to adjuvant chemotherapy in patients with HER2-overexpressing breast cancer. Notwithstanding the significance of this molecular target, the discovery of the estrogen receptor (ER) may be of even greater importance. Although tamoxifen has long been considered the hormonal therapy of choice for patients with estrogen-responsive breast cancer, accumulating clinical data suggest the new generation of aromatase inhibitors (AIs) is more effective and less toxic. With the availability of new information, guidelines have been updated and reformulated regarding the use of AIs as first-line hormonal therapy in postmenopausal women with ER-positive breast cancer. This paper, a product of the ongoing advances in oncology, incorporates two distinct, yet important, features of oncology; first, clinical concepts related to hormone-dependent breast cancer and second, pharmacoeconomic evaluation of the antiestrogen tamoxifen and the new generation of antiaromatase agents.

Pharmacoeconomic aspects of adjuvant anastrozole or tamoxifen in breast cancer: a Slovenian perspective.

New treatment approaches that include the use of aromatase inhibitors in adjuvant breast cancer management are associated with higher efficacy and increased drug costs. Our aim was to calculate the difference in total costs of care associated with two therapeutic options, anastrozole and tamoxifen, from the perspective of a healthcare provider. The cost of care and a decision tree analysis were used in this assessment. The efficacy of both drugs in terms of relapse rate was obtained from an ATAC (Arimidex, Tamoxifen Alone or in Combination) trial after the median observational time of 68 months. The total sum of all direct healthcare costs over a 60-month period was 14,438 and 8,009 Euros per person in the anastrozole and tamoxifen arm, respectively. Despite higher total costs of care associated with anastrozole, the drug cost ratio of anastrozole/tamoxifen=8.1/1 converted to a ratio of only 1.75/1 in favor of tamoxifen when costs of recurrence and adverse events were included. The total costs of care, including disease recurrences and adverse event management obtained in our analysis were similar to total costs of care values for other surveys, which lead us to believe that anastrozole is also a cost-effective alternative to tamoxifen in Slovenia.

Chemoprevention: drug pricing and mortality: the case of tamoxifen.

BACKGROUND: Tamoxifen is a prototypic cancer chemopreventive agent, yet clinical trials have not evaluated its effect on mortality or the impact of drug pricing on its cost-effectiveness. METHODS: A state-transition Markov model for a hypothetical cohort of women age 50 years was used to evaluate the effects of tamoxifen on mortality and tamoxifen price on cost-effectiveness. Incidence and mortality rates for breast and endometrial cancers were derived from Surveillance, Epidemiology and End Results statistics, and noncancer outcomes were obtained from published studies. Relative risks of outcomes were derived from the National Surgical Adjuvant Breast and Bowel Project P-1 trial. Costs were based on Medicare reimbursements. RESULTS: Projected overall mortality for women at 1.67% 5-year breast cancer risk showed little difference with or without tamoxifen, resulting in a cost-effectiveness ratio of $1,335,690 per life-year saved as a result of tamoxifen use. Adjusting for the differential impact of estrogen receptor-negative cancers, tamoxifen increased mortality for women with a uterus until the 5-year breast cancer risk reached > or =2.1%. Assigning the Canadian price for tamoxifen dramatically reduced the incremental cost (to $123,780 per life-year saved). At that price, the use of tamoxifen was less costly and more effective for women with 5-year breast cancer risks >4%. CONCLUSIONS: Tamoxifen may increase mortality in women at the lower end of the "high-risk" range for breast cancer. If prices in the U.S. approximated Canadian prices, then tamoxifen use for breast cancer risk reduction in women with a 5-year risk >3% could be a reasonable strategy to reduce the incidence of breast cancer. Because they are used by many unaffected individuals, the price of chemopreventive agents has a major influence on their cost-effectiveness.

Pharmacoeconomic analysis of adjuvant therapy with exemestane, anastrozole, letrozole or tamoxifen in postmenopausal women with operable and estrogen receptor-positive breast cancer.

OBJECTIVE: To compare the efficiency of adjuvant therapy with aromatase inhibitors or with tamoxifen in postmenopausal women with operable breast cancer and positive estrogen receptors. MATERIAL AND METHODS: A cost-utility analysis was performed based on a Markov model, from the Spanish National Health Care System perspective, comparing the treatment with exemestane (EXE: 25 mg/day) or tamoxifen (TAM: 20 mg/day) after 2-3 years of monotherapy with TAM; anastrozole (ANA, 1 mg/day) or TAM (20 mg/day) without previous TAM therapy; and letrozole (LET: 2.5 mg/day) or placebo after 5 years of monotherapy with TAM. The follow-up of a hypothetical cohort of women starting treatment at 63 years of age was simulated during 10 and 20 years. The probabilities of transition between health states and quality adjusted life years (QALYs) were obtained from the literature, and the unit costs (euro corresponding to 2004) from a Spanish database. RESULTS: After 10 and 20 years of follow-up, more QALYs per patient would be gained with the EXE scheme (0.230-0.286 and 0.566-0.708, respectively) than with ANA (0.114 and 0.285) and LET (0.176 and 0.474). The cost of gaining one QALY was lower with the EXE scheme (50,801-62,522 euro and 28,849- 35,371 euro, respectively) than with ANA (104,272 euro and 62,477 euro) and LET (91,210 euro and 49,460 euro). The result was stable for the cost per life-year gained (LYG) and in the sensitivity analysis. CONCLUSIONS: The EXE scheme after TAM is more cost-effective than the ANA and LET schemes.

Benefit and projected cost-effectiveness of anastrozole versus tamoxifen as initial adjuvant therapy for patients with early-stage estrogen receptor-positive breast cancer.

BACKGROUND: Women who have estrogen receptor (ER)-positive disease with postmenopausal onset and who receive tamoxifen as standard adjuvant treatment constitute the largest subgroup of patients with breast cancer. Recent data from the ATAC ('Arimidex, Tamoxifen Alone or in Combination') randomized trial indicate that anastrozole significantly reduces breast cancer recurrence rates but does not provide any advantage in terms of survival at 4 years posttreatment. Furthermore, anastrozole and tamoxifen were found to have different toxicity profiles. The goals of the current study were to estimate the disease-free survival (DFS) rates and potential survival benefits associated with anastrozole use and to determine whether the incremental cost-effectiveness (ICE) was low enough to warrant an immediate switch to the use of this agent, as the long-term conclusions of the ATAC trial will not be available for several years. METHODS: A computer simulation model assessed the outcomes of 64-year-old women with ER-positive breast cancer who subsequently received either anastrozole or tamoxifen for 5 years. Daily recurrence risks, as well as the relative risks associated with various treatment-related events, were calculated using data from the ATAC trial. Study endpoints included breast cancer recurrence-free survival, anticipated survival resulting from an anastrozole-induced decrease in systemic disease recurrence rates, and survival adjusted for quality of life and for hip fracture risk over periods of 4, 12, and 20 years. RESULTS: After 4 years, the projected DFS benefit associated with anastrozole was 14 days, with an ICE of $167,500 per year. Projected 12 and 20 years into the future, DFS benefits increased to 2.9 months and 5.3 months, respectively. The corresponding benefits in terms of overall survival were 0.9 months and 2.0 months, respectively, with the ICE becoming < $100,000 per life year once the projection horizon exceeded 12 years. The inclusion of quality-of-life weightings for nonfatal outcomes modestly favored anastrozole in the short term; however, if anastrozole use is associated with an increased risk of hip fracture, then the long-term benefit associated with this agent is reduced by approximately 25%. CONCLUSIONS: Adjuvant anastrozole is projected to result in a substantial improvement in DFS for patients with breast cancer. If this DFS benefit were to ultimately lead to a survival benefit, then the ICE of anastrozole use would be acceptable for patients expected to live longer than 12 years. Decision models are useful for generating realistic projections for stakeholders who are considering competing options that impact survival and quality of life and have associated societal costs.

[Disseminated carcinoma of the prostate: monotherapy or complete androgenic blockade?]. / Carcinoma de próstata diseminado ?monoterapia o bloqueo androgénico completo?

OBJECTIVES: To review the different modalities of hormonal therapy in the treatment of prostatic cancer and to analyze the results achieved by monotherapy and total androgen blockade. METHODS: The results of different studies published in the literature are reviewed, with special reference to the results of the more important randomized studies. RESULTS/CONCLUSIONS: Hormone suppression achieves a response rate of more than 75% and is therefore a valid alternative in the management of metastatic cancer of the prostate. Monotherapy and total androgen blockade have similar survival rates and disease free intervals. However, the results according to prognostic groups are significantly better for those treated with total androgen blockade and has less severe disease, suggesting early treatment.