Cost-effectiveness of fulvestrant 250 mg versus 500 mg in postmenopausal women with estrogen receptor-positive metastatic breast cancer and disease progression after antiestrogen therapy.

PURPOSE: To determine the cost-effectiveness of fulvestrant 250 mg compared to 500 mg in postmenopausal women with estrogen receptor-positive metastatic breast cancer and disease progression after antiestrogen therapy. METHODS: A Markov model was constructed to find the incremental cost-effectiveness of fulvestrant 250 mg monthly when compared with the 500 mg monthly in patients with progression after antiestrogen therapy. The model duration was 24 months. Clinical efficacy data inputs were derived from a phase III clinical trial demonstrating a statistically significant increase in progression-free survival in patients receiving 500 mg versus 250 mg. Cost data utilized were all relevant Ambulatory Payment Classification payment rates from the 2011 Medicare Outpatient Prospective Payment System. A Monte Carlo simulation was performed to test the model at various willingness to pay thresholds. RESULTS: The incremental cost-effectiveness ratio as determined by the Markov model was US$10,972 per month of progression-free survival for the 500 mg dose compared with the 250 mg dose. Using a Monte Carlo simulation, it was found that 500 mg monthly was cost-effective at and above the willingness to pay threshold of US$15,000 per month. A series of one-way sensitivity analyses showed this result is robust to geographical practice variations in costs of drug administration and physician examination. CONCLUSION: From a third party payer perspective, the value of fulvestrant 500 mg monthly is dependent on the willingness to pay threshold. Despite a labeling change for fulvestrant in September 2010, fulvestrant 250 mg monthly appears to be a viable option in the target population.

First-line Treatment with Ribociclib plus Endocrine Therapy for Premenopausal Women with Hormone-receptor-positive Advanced Breast Cancer: A Cost-effectiveness Analysis.

BACKGROUND: We conducted a cost-effectiveness analysis incorporating recent phase III clinical trial (MONALEESA-7) data to evaluate the cost-effectiveness of ribociclib (RIB) as a first-line treatment for premenopausal women with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from the United States healthcare payer perspective. In addition, because RIB has not been marketed in China, we identified the range of drug costs for which RIB could be considered cost effective from a Chinese healthcare system perspective. PATIENTS AND METHODS: A Markov model was developed to evaluate the cost-effectiveness of adding RIB to endocrine therapy over a lifetime. The clinical outcomes and utility data were obtained from published literature. Costs data were obtained from United States and Chinese official websites, and we determined the potential price for RIB in China based on its price in the United States. The main outcomes of this study were the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs). RESULTS: The model projected that mean outcome was better with RIB and endocrine combined (3.83366 QALYs) than with endocrine therapy alone (2.71203 QALYs). In the United States, RIB and endocrine therapy cost an additional $604,960.06, resulting in an ICER of $539,357.95/QALY compared with endocrine monotherapy. Subgroup analyses indicated that, in China, the projected mean outcomes were better for RIB and endocrine therapy (6.37 QALYs) than for endocrine monotherapy (2.71 QALYs). The corresponding incremental costs were $224,731.88943. Thus, the ICER comparing RIB and endocrine therapy with endocrine therapy alone represented a $61,454.96/QALY gain. CONCLUSION: Additional use of RIB is estimated to not be cost effective as a first-line treatment for premenopausal women with HR-positive, HER2-negative ABC in the United States. A value-based price for the cost of RIB is less than $31.74/200 mg for China.

Progesterone for Prevention of Preterm Birth: Shortcomings and Unintended Consequences of the Orphan Drug Act.

Preterm birth is a problem of major public health significance that continues to plague our country despite the existence of a therapy, 17α-hydroxyprogesterone caproate, with known efficacy in reducing the risk of spontaneous preterm birth among high-risk women. Over the past several years, the Louisiana Department of Health has undertaken a robust, multifaceted initiative to improve access to 17α-hydroxyprogesterone caproate, which resulted in a 3.5-fold increase in the percentage of eligible high-risk pregnant women in the Medicaid program who received the therapy between 2013 and 2016. Yet despite Louisiana's progress, the vast majority of the eligible population still fails to receive 17α-hydroxyprogesterone caproate. In this Current Commentary, we argue that the high price of progesterone since U.S. Food and Drug Administration approval has unnecessarily complicated access, and our nation has potentially suffered nearly 60,000 avoidable premature births as a consequence. We present the history of the orphan drug approval and manufacturer-imposed price increase for injectable progesterone, the interplay between the drug's high price and the persistence of racial and ethnic disparities in preterm birth, which are particularly germane in Louisiana, and Louisiana's broad-reaching efforts to improve progesterone coverage. The story of 17α-hydroxyprogesterone caproate highlights the durable barriers that high prices place in the way of access and helps illuminate the shortcomings and unintended consequences of the Orphan Drug Act. This case, however, is not an outlier; it is the far-too-common product of monopoly pricing in the U.S. pharmaceutical market, inadvertently bolstered by existing law, at the expense of affordability and patient access.

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.

Factors Associated with Adherence to Adjuvant Endocrine Therapy Among Privately Insured and Newly Diagnosed Breast Cancer Patients: A Quantile Regression Analysis.

BACKGROUND: Adherence to adjuvant endocrine therapy (AET) for estrogen receptor-positive breast cancer remains suboptimal, which suggests that women are not getting the full benefit of the treatment to reduce breast cancer recurrence and mortality. The majority of studies on adherence to AET focus on identifying factors among those women at the highest levels of adherence and provide little insight on factors that influence medication use across the distribution of adherence. OBJECTIVE: To understand how factors influence adherence among women across low and high levels of adherence. METHODS: A retrospective evaluation was conducted using the Truven Health MarketScan Commercial Claims and Encounters Database from 2007-2011. Privately insured women aged 18-64 years who were recently diagnosed and treated for breast cancer and who initiated AET within 12 months of primary treatment were assessed. Adherence was measured as the proportion of days covered (PDC) over a 12-month period. Simultaneous multivariable quantile regression was used to assess the association between treatment and demographic factors, use of mail order pharmacies, medication switching, and out-of-pocket costs and adherence. The effect of each variable was examined at the 40th, 60th, 80th, and 95th quantiles. RESULTS: Among the 6,863 women in the cohort, mail order pharmacies had the greatest influence on adherence at the 40th quantile, associated with a 29.6% (95% CI = 22.2-37.0) higher PDC compared with retail pharmacies. Out-of-pocket cost for a 30-day supply of AET greater than $20 was associated with an 8.6% (95% CI = 2.8-14.4) lower PDC versus $0-$9.99. The main factors that influenced adherence at the 95th quantile were mail order pharmacies, associated with a 4.4% higher PDC (95% CI = 3.8-5.0) versus retail pharmacies, and switching AET medication 2 or more times, associated with a 5.6% lower PDC versus not switching (95% CI = 2.3-9.0). CONCLUSIONS: Factors associated with adherence differed across quantiles. Addressing the use of mail order pharmacies and out-of-pocket costs for AET may have the greatest influence on improving adherence among those women with low adherence. DISCLOSURES: This research was supported by a Ruth L. Kirschstein National Research Service Award for Individual Predoctoral Fellowship grant from the National Cancer Institute (grant number F31 CA174338), which was awarded to Farias. Additionally, Farias was funded by a Postdoctoral Fellowship at the University of Texas School of Public Health Cancer Education and Career Development Program through the National Cancer Institute (NIH Grant R25 CA57712). The other authors declare no conflicts of interest. DISCLAIMER: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Farias was primarily responsible for the study concept and design, along with Hansen and Zeliadt and with assistance from the other authors. Farias, Hansen, and Zeliadt took the lead in data interpretation, assisted by the other authors. The manuscript was written by Farias, along with Thompson and assisted by the other authors, and was revised by Ornelas, Li, and Farias, with assistance from the other authors.

Economic and cost-effectiveness issues in breast cancer treatment.

The need for cost-effectiveness analyses is based on the unfortunate but universal situation of limited financial resources that ideally should be used to maximal benefit. Formal cost-effectiveness analyses assume a societal utilitarian perspective with the objective of maximizing net health benefit for members of a population within a limited level of resources. This societal perspective is in stark contrast to the clinician's perspective, whose goal is to maximize his or her patient's health status (no matter what effect those decisions have on other patients or resources). This difference in perspective and objectives explains why many clinicians object to the use of cost-effectiveness analysis in setting policies. When considering the natural history of breast cancer from screening, evaluation of suspicious lesions, primary therapy, staging, adjuvant therapy, monitoring, metastatic disease, and palliative care, it is striking that most cost-effectiveness studies have been related to screening or the use of adjuvant drug therapies. In prior work our group has shown that the use of chemotherapy in node-negative breast cancer and of tamoxifen alone or in combination with chemotherapy in premenopausal women are cost-effective compared with other common medical treatments. Given the increasing pressure to contain costs in contemporary medicine, one should remember that cost effectiveness is related to value, value defined as quality/costs. Examples are discussed when the controversy focuses on increasing quality (eg, valued outcomes, such as additional years of life or years of breast preservation) and on controlling costs (eg, integrating multidisciplinary care, minimizing superfluous testing, or reducing surgical biopsy rates). Efforts should be directed at both sides of this ratio.

Cost-effectiveness of raloxifene and hormone replacement therapy in postmenopausal women: impact of breast cancer risk.

OBJECTIVE: To examine the life expectancy and cost-effectiveness of hormone replacement therapy (HRT) and raloxifene therapy in healthy 50-year-old postmenopausal women. METHODS: We performed a cost-effectiveness analysis using a Markov model, discounting the value of future costs and benefits to account for their time of occurrence. RESULTS: Both HRT and raloxifene therapy increase life expectancy and are cost-effective relative to no therapy for 50-year-old postmenopausal women. For women at average breast cancer and coronary heart disease risk, lifetime HRT increases quality-adjusted life expectancy more (1.75 versus 1.32 quality-adjusted life years) and costs less ($3802 versus $12,968) than lifetime raloxifene therapy. However, raloxifene is more cost-effective than HRT for women at average coronary risk who have a lifetime breast cancer risk of 15% or higher or who receive 10 years or less of postmenopausal therapy. Raloxifene is also the more cost-effective alternative if HRT reduces coronary heart disease risk by less than 20%. CONCLUSIONS: Assuming the benefit of HRT in coronary heart disease prevention from observational studies, long-term HRT is the most cost-effective alternative for women at average breast cancer and coronary heart disease risk seeking to extend their quality-adjusted life expectancy after menopause. However, raloxifene is the more cost-effective alternative for women at average coronary risk with one or more major breast cancer risk factors (first-degree relative, prior breast biopsy, atypical hyperplasia or BRCA1/2 mutation). These results can help inform decisions about postmenopausal therapy until the results of large scale randomized trials of these therapies become available.

Modeling the annual costs of postmenopausal prevention therapy: raloxifene, alendronate, or estrogen-progestin therapy.

OBJECTIVE: To estimate the annual cost and outcome impacts attributable to raloxifene, alendronate, and estrogen-progestin therapy as prevention therapies among postmenopausal women over the first 7 years of hormone replacement therapy (HRT). METHODS: A budget-impact model was devised to compare the costs, benefits, and costs per event avoided for various postmenopausal therapies (raloxifene, alendronate, or estrogen-progestin combination therapy), compared to no intervention, taking into account the persistency rates. Net costs are direct medical costs attributable to treatments relative to no intervention. Net benefits are defined as the number of events avoided as a result of therapy. The main outcome measures are annual total net costs, net benefits, and costs per event avoided compared to no intervention among postmenopausal white women with intact uteri and normal baseline risks for osteoporotic hip or vertebral fractures, fatal or nonfatal myocardial infarction, and breast cancer. Data and model assumptions are based on clinical trial data and published retrospective studies. RESULTS: The average annual net cost of therapy declines after the first year of therapy for all interventions, primarily due to discontinuation, and continues to decline over time due to savings in medical costs for events avoided. Net events avoided are greater for raloxifene than alendronate, but HRT use results in net harm. The cost per event avoided is lower for raloxifene than alendronate. Improved persistence improves the cost-effectiveness for both interventions. Sensitivity analyses indicate the model results are most sensitive to the assumed impact of raloxifene on coronary heart disease and breast cancer risk. Alendronate as a prevention intervention is dominated by raloxifene under almost all model scenarios. CONCLUSION: The annual cost of long-term postmenopausal prevention therapy is highest during the first few years of therapy. Long-term prevention does not provide a return on investment in fewer than 3 years, but savings in medical costs partially offset intervention costs after 2 years. For postmenopausal women, pharmacologic interventions with multiple prevention benefits tend to be more cost effective than interventions with a single source of health benefit.

A randomised controlled trial of microwave endometrial ablation without endometrial preparation in the outpatient setting: patient acceptability, treatment outcome and costs.

OBJECTIVE: To compare outpatient microwave endometrial ablation (MEA) in the postmenstrual phase to standard MEA treatment after drug preparation in a day case theatre environment. DESIGN: A randomised controlled trial. SETTING: A large United Kingdom teaching hospital. POPULATION: Two hundred and ten women complaining of excessive menstrual loss. METHODS: Two hundred and ten women with excessive menstrual loss were randomised. Ninety-seven women were treated as outpatients in the immediate post-menstrual phase and 100 were treated in an operating theatre after hormonal preparation. All procedures were commenced under local anaesthesia with or without conscious sedation. Analysis was by modified intention to treat. MAIN OUTCOME MEASURES: Primary outcome measures were satisfaction with treatment (measured at one year) and acceptability of treatment (measured at two weeks). Secondary outcome measures were menstrual outcome and financial cost. RESULTS: Significantly more women found treatment post-menses acceptable; 86 (89.5%) versus 76 (76.0%) [difference in proportions 13.6%, 95% CI (3.0%, 23.9%)]. Similar numbers in each arm were totally or generally satisfied with the treatment, 86 (92.5%) versus 84 (88.4%) [difference in proportions 4.1%, 95% CI (-4.7%, 12.9%)] while amenorrhoea rates at one year were comparable, 52 (55.9%) versus 60 (61.9%). [difference in proportions -5.9%, 95% CI (-19.8%, 7.6%)]. The mean health service costs were 124 pounds (95% CI 86-194 pounds) lower for the patients in the post-menses group. CONCLUSION: MEA performed under local anaesthesia (with or without conscious sedation) in the post-menstrual phase achieves high levels of satisfaction is very acceptable to patients and results in significantly reduced health service costs. Importantly menstrual outcomes are not affected by omission of drug preparation. There is now good evidence to support the use of MEA, without drug endometrial preparation, in the outpatient setting.

Cost-effectiveness of raloxifene in the UK: an economic evaluation based on the MORE study.

Raloxifene treatment has been shown to reduce the risk of vertebral fractures and breast cancer in postmenopausal women. The long-term economic implications of treatment with raloxifene have not yet been investigated. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women in the UK with raloxifene. A previously developed computer simulation model was used to estimate the cost-effectiveness of osteoporotic treatments with extra skeletal benefits. The model was populated with epidemiological data and cost data relevant for a UK female population. Data on the effect of treatment were taken from the Multiple Outcomes of Raloxifene (MORE) study, which recruited women with low bone mineral density or with a prior vertebral fracture. Cost-effectiveness was estimated using Quality Adjusted Life Years (QALYs) and life years gained as primary outcome measures. The cost per QALY gained of treating postmenopausal women without prior vertebral fractures was 18,000 pounds, 23,000 pounds , 18,000 pounds and 21,000 pounds at 50, 60, 70 and 80 years of age. Corresponding estimates for women with prior vertebral fractures were 10,000 pounds, 24,000 pounds, 18,000 pounds and 20,000 pounds. In relation to threshold values that are recommended in the UK, the analysis suggests that raloxifene is cost-effective in the treatment of postmenopausal women at an increased risk of vertebral fractures.

First-line endocrine treatment of breast cancer: aromatase inhibitor or antioestrogen?

Until recently, endocrine therapy for breast cancer was relatively simple. If the tumour expressed hormone receptors, regardless of stage and age, tamoxifen was indicated. While this largely remains the case for premenopausal women, clinical trials in postmenopausal women have broadened our choice to include one of three selective aromatase inhibitors (AIs), the nonsteroidal agents anastrozole or letrozole and the steroidal agent exemestane. Comparative data concerning the efficacy, toxicity, tolerability and cost of AI vs tamoxifen continues to evolve with over 40 000 women slated to be involved in clinical trials. Currently, tamoxifen remains an appropriate choice for adjuvant treatment, and will remain so unless a clear survival advantage emerges for adjuvant AI therapy. However, anastrozole is widely seen as a useful alternative, with particular merit for patients prone to the development of serious tamoxifen side effects. For endocrine therapy naïve advanced disease, several trials have provided evidence that a nonsteroidal AI has replaced tamoxifen as optimal treatment. In the neoadjuvant setting, letrozole was also more effective than tamoxifen, both in terms of response rates and the incidence of breast-conserving surgery, and so AI therefore also dominates this evolving indication. The ongoing adjuvant clinical trials ask all the relevant questions regarding tamoxifen and AI in combination, sequence and duration, except for 5 years of an AI vs a longer period. For both the advanced and early-stage disease, resistance remains the key obstacle to overcome, and trials that combine endocrine agents with signal transduction inhibitors such as HER1 and HER2 kinase inhibitors, farnesyl transferase inhibitors, mTOR inhibitors as well as COX2 inhibitors are being developed in a concerted attempt to address this problem.

Economic evaluation of endocrine therapy in the treatment of breast cancer.

Endocrine therapy has become an integral part of the management of breast cancer and its different clinical applications raise different economic issues. The low toxicity, good response and relatively low cost of agents makes endocrine therapy an attractive treatment option for breast cancer patients at different stages of their disease. The method, hypotheses and expectations from economic analysis of endocrine therapy depend on the objectives of treatment (preventive, curative or palliative), the therapies being compared, the population being treated and the clinical benefits expected. The economic and quality of life literature has focused mainly on the analysis of endocrine therapy in the adjuvant setting. As budgets continue to shrink and treatment guidelines become challenged by new therapeutic and preventive approaches, decision analysis in breast cancer management is likely to become more explicit. Economic analysis can be a useful tool to guide clinical decisions in the management of this complex and chronic disease. Ultimately, the positioning of endocrine therapy with respect to other complementary or alternative treatment modalities will depend on the level of expected effectiveness, and on finding the best therapeutic solution to meet the breast cancer patient's clinical situation, expectations and needs.

Prophylactic laparoscopic ovarian ablation for premenopausal breast cancer: medical and economic efficacy.

Worldwide analysis showed a highly significant reduction in the annual rates both of recurrence and of death produced by ovarian ablation. We examined the safety, efficacy, and cost-effectiveness of prophylactic laparoscopic oophorectomy for premenopausal breast cancer. Prophylactic laparoscopic oophorectomy was attempted in 15 selected premenopausal patients with breast cancer. After mastectomy, these patients had laparoscopic ovarian ablation as treatment for breast carcinoma with positive estrogen receptors. To evaluate the economic impact of laparoscopic oophorectomy, comparisons were made between patients treated laparoscopically and those treated with conventional surgery, chemotherapy, and hormonal therapy. The average time required for laparoscopic bilateral oophorectomy was 44 min. Oral intake was resumed the next morning, and the patients were discharged 3 days after surgery. No limitation on physical activity and no complications were required during postoperative days. There was no reduction in the overall costs of laparoscopic surgery and conventional surgery in Japan. The cost of one year's supply of tamoxifen was equivalent to the overall cost of surgical oophorectomy. From medical and economic viewpoints, we conclude that laparoscopic ovarian ablation should be considered an alternative to adjuvant chemotherapy in premenopausal women.