Cost-effectiveness of letrozole in the extended adjuvant treatment of women with early breast cancer.

Adjuvant tamoxifen therapy for 5 years reduces recurrence in hormone receptor positive, post-menopausal women with early breast cancer, but offers no advantage when prolonged to another 5 years, during which the risk of recurrence remains high. Treating patients, who remain disease-free after 5 years of tamoxifen, with letrozole significantly reduces recurrence, regardless of nodal status. This study evaluated the life-time cost-utility of extended adjuvant letrozole therapy in 62-year-old patients from a third-party payer perspective. A Markov model incorporated locoregional, contralateral, and metastatic recurrences. The comparator was placebo. Event rates were based on published trials. Utility values were taken from a clinical trial and published literature. Costs were obtained from published literature, provincial payment schedules, cancer agencies, and drug plans formularies. Resource use reflected Canadian treatment patterns. Robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Extended adjuvant letrozole therapy of a cohort consisting of 50% node-negative and 50% node-positive patients prolonged their lives on average by 0.466 years or 0.267 quality-adjusted life years (QALYs) at an additional cost of Can$8,031 per patient, yielding an incremental cost-utility ratio (ICUR) of $34,058 per QALY. Letrozole was more cost-effective in node-positive than in node-negative patients (Can$26,553 vs Can$46,049 per QALY). Results were robust to variations in age, healthcare costs, and utilities. The degree of confidence that the cost per QALY would be below Can$50,000 reached 100% for node-positive and 77% for node-negative patients. Extended adjuvant letrozole is cost-effective in both node-negative and node-positive patients having ICURs below Can$50,000/QALY.

Retrospective study of the effect of skeletal complications on total medical care costs in patients with bone metastases of breast cancer seen in typical clinical practice.

Intravenous bisphosphonates are effective in reducing the incidence of skeletal-related events (SREs) in women with bone metastases of breast cancer. The cost-effectiveness of such therapy depends in part on the potential cost savings achieved by preventing these events. However, estimates of the costs of SREs in women with bone metastases of breast cancer in typical US clinical practice are unavailable. The purpose of this study was to estimate the treatment costs of clinically significant SREs and the impact of these events on total medical care costs in patients with bone metastases of breast cancer. Data were gathered from a large US health insurance claims database. Patients with bone metastases of breast cancer who experienced one or more clinically significant SREs in typical clinical practice were matched to similar patients without SREs based on propensity scores. Kaplan-Meier estimated total medical care costs were compared over 60 months for propensity-matched samples of patients with SREs and without SREs. We identified 617 patients with breast cancer and bone metastases, including 321 (52%) with > or = 1 clinically significant SRE. After matching, there were 201 patients each in the SRE and no-SRE groups, with mean follow-up of 13.8 and 11.0 months, respectively. In the SRE group, costs of treatment of SREs were $13,940 (95% CI, $11,240-$16,856) per patient. Total medical care costs were $48,173 (95% CI, $19,068-$77,684) greater in SRE versus no-SRE patients (P = 0.001). The costs of clinically significant SREs in patients with breast cancer and bone metastases seen in typical clinical practice are substantial. Treatments that reduce the incidence of SREs, such as intravenous bisphosphonates, should reduce these costs.

Cost-effectiveness of extended adjuvant letrozole therapy after 5 years of adjuvant tamoxifen therapy in postmenopausal women with early-stage breast cancer.

OBJECTIVE: To estimate the cost-effectiveness of extended adjuvant letrozole in postmenopausal women with early breast cancer and estrogen or progesterone receptor-positive tumors who had completed 5 years of adjuvant tamoxifen. STUDY DESIGN: Cost-effectiveness analysis using a Markov model. METHODS: Using a Markov model, we estimated the incremental cost per quality-adjusted life-year (QALY) gained with extended adjuvant letrozole vs no extended adjuvant therapy. Probabilities of breast cancer recurrence or new contralateral tumor adverse effects and death were estimated using data from the MA.17 study and other secondary sources. Costs (in 2004 US dollars) and quality-of-life effects (utilities) of breast cancer events and adverse effects were derived from the literature. RESULTS: In base-case analyses, extended adjuvant letrozole vs no extended adjuvant therapy results in an expected gain of 0.34 QALYs per patient (13.62 vs 13.28 QALYs), at an additional lifetime cost of 9699 dollars per patient (55,254 dollars vs 45,555 dollars). The incremental cost per QALY gained with letrozole is 28,728 dollars. Cost-effectiveness is sensitive to the assumed reduction in risk of breast cancer events with letrozole but is insensitive to the risks, costs, and quality-of-life effects of osteoporosis and hip fracture. Cost-effectiveness is less than 100,000 dollars per QALY for node-positive patients younger than 81 years and for node-negative patients younger than 73 years. CONCLUSION: For postmenopausal women with early breast cancer who have completed 5 years of adjuvant tamoxifen, the cost-effectiveness of extended adjuvant letrozole is within the range of other generally accepted medical interventions in the United States.

Cost effectiveness of extended adjuvant letrozole in postmenopausal women after adjuvant tamoxifen therapy: the UK perspective.

BACKGROUND: MA17 was a randomised placebo-controlled trial of letrozole 2.5 mg/day in 5187 estrogen receptor-positive, 50% node-negative, postmenopausal women (median age 62 years at enrollment) with early breast cancer, post-5 years' adjuvant tamoxifen therapy. The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting. METHODS: A Markov model was used to estimate the incremental cost per QALY gained with extended adjuvant letrozole versus no therapy. Probabilities of disease progression and death were estimated using data from the MA17 study and other secondary sources. Costs of breast cancer care (letrozole therapy, surveillance, recurrences, terminal care) and treatment of osteoporosis and utilities were derived from literature. A full probabilistic sensitivity analysis was undertaken. The analysis was conducted from the perspective of the UK National Health Service (NHS) and cost estimates reflect 2004 values. All costs and outcomes were discounted at 3.5%. RESULTS: Extended adjuvant letrozole resulted in a gain of 0.36 QALYs per patient (13.66 vs 13.30 with no therapy). These benefits were obtained at an additional expected lifetime cost of 3732 pounds per patient (10,833 pounds letrozole vs 7101 pounds with no therapy). Cost effectiveness was estimated at 10,338 pounds per QALY gained (95% CI 5276, 43,828). The results were robust to sensitivity analyses. CONCLUSION: Five years of letrozole therapy appears to be cost effective from the NHS perspective and should be considered in women with early breast cancer, following tamoxifen adjuvant therapy.

Risk of clinical fractures after gonadotropin-releasing hormone agonist therapy for prostate cancer.

PURPOSE: We assessed the relationship between GnRH agonists and the risk of clinical fractures in men with prostate cancer. MATERIALS AND METHODS: Using a database of medical claims from 16 large American companies we identified a study group of 3,779 men with prostate cancer who received treatment with a GnRH agonist and a control group of 8,341 with prostate cancer who were not treated with a GnRH agonist. Men with 1 or more medical claims for bone metastases were excluded. The rates of any clinical fracture, hip fracture and vertebral fracture were compared between the groups. RESULTS: The rate of any fracture was 7.91/100 vs 6.55/100 person-years at risk in men who received vs did not receive a GnRH agonist (relative risk 1.21, 95% CI 1.09 to 1.34). The rates of hip fracture (relative risk 1.76, 95% CI 1.33 to 2.33) and vertebral fracture (relative risk 1.18, 95% CI 0.94 to 1.48) were also higher in men who received a GnRH agonist. GnRH agonist treatment was independently associated with fracture risk on multivariate analyses. CONCLUSIONS: GnRH agonists increase the risk of clinical fracture in men with prostate cancer.

Impact of skeletal complications on total medical care costs among patients with bone metastases of lung cancer.

INTRODUCTION: Previous studies have estimated the costs of skeletal-related events (SREs) for patients with bone metastases of solid tumors by tallying costs for services specifically attributable to these events. This approach may underestimate costs if SREs indirectly increase use of other services. METHODS: This is a retrospective observational study using a large health insurance claims database. Patients with bone metastases of lung cancer who experienced > or =1 SRE were matched to similar patients without SREs based on propensity scores. Kaplan-Meier estimated total medical care costs were compared for propensity-matched samples of patients with SREs and without SREs. RESULTS: We identified 534 patients with lung cancer and bone metastases, including 295 (55%) with > or =1 SRE. After matching, there were 162 patients each in the SRE and no-SRE groups with mean follow-up of 5.3 and 3.9 months, respectively. In the SRE group, costs of treatment of SREs were $9,480 (95% CI $7,625 to $11,374) per patient. Total medical care costs were $27,982 (95% CI $15,921 to $40,625) greater for SRE versus no-SRE patients (p < 0.001). CONCLUSIONS: The costs of SREs in patients with lung cancer and bone metastases are substantial and potentially greater than previously estimated.

Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer.

PURPOSE: Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density, a surrogate for fracture risk, in men with prostate cancer. We conducted a claims-based cohort study to characterize the relationship between GnRH agonists and risk for clinical fractures in men with nonmetastatic prostate cancer. PATIENTS AND METHODS: Using medical claims data from a 5% national random sample of Medicare beneficiaries, we identified a study group of men with nonmetastatic prostate cancer who initiated GnRH agonist treatment from 1992 to 1994 (n = 3,887). A comparison group of men with nonmetastatic prostate cancer who did not receive GnRH agonist treatment during the study period (n = 7,774) was matched for age, race, geographic location, and comorbidity. Clinical fractures were identified using inpatient, outpatient, and physician claims during 7 years of follow-up. RESULTS: In men with nonmetastatic prostate cancer, GnRH agonists significantly increased fracture risk. The rate of any clinical fracture was 7.88 per 100 person-years at risk in men receiving a GnRH agonist compared with 6.51 per 100 person-years in matched controls (relative risk, 1.21; 95% CI, 1.14 to 1.29; P < .001). Rates of vertebral fractures (relative risk, 1.45; 95% CI, 1.19 to 1.75; P < .001) and hip/femur fractures (relative risk, 1.30; 95% CI, 1.10 to 1.53; P = .002) were also significantly higher in men who received a GnRH agonist. GnRH agonist treatment independently predicted fracture risk in multivariate analyses. Longer duration of treatment conferred greater fracture risk. CONCLUSION: GnRH agonists significantly increase risk for any clinical fracture, hip fractures, and vertebral fractures in men with prostate cancer.

Natural history of bone complications in men with prostate carcinoma initiating androgen deprivation therapy.

BACKGROUND: As evidence accumulates in favor of androgen deprivation therapy (ADT) in patients with recurrent or metastatic prostate carcinoma, concern has increased regarding bone loss associated with therapeutic hypogonadism. The current study described the natural history of bone complications in men with prostate carcinoma who have initiated ADT. METHODS: Using 1992-2001 claims data from a 5% national random sample of Medicare beneficiaries, the authors identified men with prostate carcinoma who initiated ADT between 1992 and 1994. They analyzed inpatient, outpatient, and physician claims for bone complications over 7 subsequent years. They stratified the quartile of patients who survived longest into 2 cohorts: those who had received ADT for longer than and those who had received ADT for shorter than the median of 697 days. They evaluated the cumulative proportions of patients in each cohort with claims for pathologic fractures, osteoporosis/osteopenia, and nonpathologic fractures. RESULTS: In the 1992-1994 sample, 4494 men with prostate carcinoma initiated ADT. Of these, 1126 survived > 2028 days (5.5 years). During the first 3 years of evaluation, the proportion of bone events was similar for men with shorter durations of ADT and men with longer durations of ADT. However, by 7 years, more men in the longer ADT cohort (45%) had sustained at least 1 pathologic or nonpathologic fracture compared with men in the shorter ADT cohort (40%). CONCLUSIONS: In the current study, men with prostate carcinoma were found to be at risk for adverse bone effects from both the disease and the treatment. These longitudinal data revealed that fractures are common in this patient population and appear to be linked to the duration of ADT.

The cost of treatment of skeletal-related events in patients with bone metastases from lung cancer.

PURPOSE: Patients with bone metastases from lung cancer often experience skeletal-related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia or pain requiring surgery, radiotherapy or opioid analgesics. These complications result in impaired mobility and reduced quality of life and have a significant negative impact on survival. The economic consequences of SREs in patients with lung cancer have not been examined. METHODS: We conducted a retrospective analysis using a large US health insurance claims database to estimate the incidence and costs of treatment of SREs in patients with bone metastases of lung cancer treated in a naturalistic setting. Study subjects had >/=2 encounters with a diagnosis of primary lung cancer and >/=2 encounters with a diagnosis of metastases to bone. SREs were identified based on the occurrence on or after the date of first diagnosis of bone metastases, of (1) >/=1 encounter with a diagnosis of pathological fracture, spinal cord compression or hypercalcemia, (2) >/=1 bone surgery or radiotherapy procedure, or (3) the initiation of opioid analgesic therapy. Survival and costs of SRE-related care in patients with SREs were estimated using Kaplan-Meier methods. RESULTS: We identified 534 patients with lung cancer and bone metastases, including 295 (55%) with >/=1 SRE. Radiotherapy (68%) and fracture (35%) were the most common SREs. Median survival after the first identified SRE was 4.1 months (95% confidence interval: 3.6-5.5 months). The estimated lifetime SRE-related cost per patient was USD 11,979 (95% confidence interval: USD 10,193-13,766). Radiotherapy accounted for the greatest proportion of cost (61%) by SRE type. CONCLUSION: The economic burden of SREs in patients with bone metastases of lung cancer is substantial. Intravenous bisphosphonates, such as zoledronic acid, which have been shown to prevent these events, may reduce these costs.

Evaluating minimal clinically important differences for the acne-specific quality of life questionnaire.

BACKGROUND: The Acne-Specific Quality of Life Questionnaire (Acne-QoL) is a responsive, reliable and valid instrument developed to measure the impact of facial acne across four dimensions of patient QOL. Score changes on this instrument have been used to report statistically significant treatment advantages for a low-dose oral contraceptive (Estrostep, containing norethisterone (norethindrone) acetate (NA) 1mg and ethinylestradiol (EE) [20, 30, 35 mg] as compared with placebo in women with moderate acne vulgaris. However, the question remained if these statistically significant results were also clinically meaningful. OBJECTIVES: To evaluate the statistically significant Acne-QoL benefits observed with NA/EE in terms of their clinical significance, and to compare the three different approaches for defining a minimal clinically important difference (MCID) for the Acne-QoL instrument. METHODS: Since the optimum method for estimating MCIDs has yet to be established, three different published approaches for determining MCIDs were applied and compared using data from two randomised, double-blind, placebo- controlled studies of the efficacy of NA/EE in the treatment of facial acne. RESULTS: Although the approaches differed substantially, the resulting MCID estimates were comparable. Specifically, the MCID estimates ranged from 0.50-10.3 mean change per item, depending on the domain. The results showed that the statistically significant treatment advantages for NA/EE were also clinically significant. CONCLUSION: When applied to the change scores present, the results showed that the statistically significant treatment advantages for NA/EE were also clinically significant.

A comparison of therapy continuation rates of different hormone replacement agents: a 9-month retrospective, longitudinal analysis of pharmacy claims among new users.

OBJECTIVE: To estimate the rate of therapy continuation among women using six different hormone replacement therapies (HRTs). DESIGN: A retrospective, longitudinal analysis of pharmacy claims data was conducted for 7,120 women who were new users of six HRT regimens. Continuation rates of therapies were examined at the end of the 9-month period. In addition, the odds ratio of continuation for each product was determined using a logistic model, which controlled for the potential influence of a patient's age and a provider's age, gender, specialty, and geographical location. RESULTS: Treatment continuation rates at the end of the 9-month period were significantly higher among patients prescribed oral 1 mg norethindrone acetate/5 microgram ethinyl estradiol (EE) (femhrt, Pfizer Inc, New York, NY, USA) compared with other HRT regimens. Patients prescribed 1 mg norethindrone acetate/5 microgram EE were 52% more likely to continue therapy compared with patients prescribed 0.625 mg conjugated equine estrogens/2.5 mg or 5 mg medroxyprogesterone acetate (Prempro, Wyeth, Madison, NJ, USA). Significantly higher rates of therapy continuation were seen in women aged 55 years or older, those who did not switch HRT during the analysis, those who received care in the central and northeast regions of the United States, and those who were seen by obstetricians/gynecologists (v primary care physicians) or female (v male) providers. CONCLUSIONS: The higher rates of treatment continuation seen with newer continuous combined HRTs, such as 1 mg norethindrone acetate/5 microgram EE, may lead to improved long-term compliance and, therefore, better protection against osteoporosis in postmenopausal women.