Active, but not passive cigarette smoking was inversely associated with mammographic density

The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism. We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Women’s Health Across the Nation (SWAN). We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked ≥20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked ≥20 cigarettes/day was associated with 23.8% lower density, compared to having smoked ≤9 cigarettes/day (p < 0.001). Our findings support the hypothesis that tobacco smoke exerts an antiestrogenic effect on breast tissue, but counters the known increased risk of breast cancer with smoking prior to first full-term birth. Thus, our data suggest that the antiestrogenic but not the carcinogenic effects of smoking may be reflected by breast density

The economic and clinical outcomes and policy implications of gene expression profiling in breast cancer care

Thesis (Ph. D.)--University of Washington, 2004In the U.S., the majority of premenopausal breast cancer patients are recommended by clinical guidelines to receive adjuvant chemotherapy to prevent disease progression and increase survival. However, low-risk patients may be experiencing the side effects of chemotherapy, with no corresponding benefit, which may also lead to spending on unnecessary treatment by healthcare payers. In response to this situation, new genomic assays have been marketed or are in development that profile the biology of the tumor cells and may be better able to identify high-risk patients than the current guidelines. However, the clinical, economic and patient outcomes associated with these approaches are unknown. We compared the cost-utility of one of these genomic assays developed by investigators at the Netherlands Cancer Institute to NIH guidelines in a cohort of 44 year-old women with early stage breast cancer. We utilized a decision analytic model that was informed by empiric and literature-based estimates, and model parameters were varied in sensitivity analyses. As an input to the decision model, the costs of adjuvant chemotherapy have a large influence on results. Thus, an accurate estimate of these costs was needed. We conducted a cost study to estimate the direct medical costs of adjuvant chemotherapy in this young patient population to inform the decision model and to better understand the economic burden of this treatment modality. We estimated these costs to be $21,684, so they constitute a substantial component of breast cancer treatment costs. For the cost-utility analysis, we found that the genomic assay was much more specific, but less sensitive than NIH guidelines in detecting high-risk women. As a result, the improvement in quality of life due to avoiding chemotherapy appeared to be offset by an increased risk of breast cancer progression. It appears that these genomic assays, which have yet to be validated or demonstrated to be in equipoise with current NIH guidelines, require additional refinement and validation before implementation in clinical practice. Our study highlights the value of cost-utility analysis in clarifying the tradeoffs between life expectancy, quality of life and costs in the era of genetic assays

Abstract PS9-54: Healthcare costs for metastatic breast cancer patients treated with human epidermal growth factor receptor 2 targeted agents

Abstract Background: Human Epidermal Growth Factor Receptor 2 positive (HER2+) breast cancer (BC) represents approximately 15% of early stage BC cases and is associated with a more aggressive clinical phenotype and poor prognosis with respect to most BC. Over the last decade new HER2-targeted therapies have become available that have prolonged survival for both early stage and metastatic breast cancer (mBC). However, the cost impact of these therapies has not been fully assessed in recent years. Given the evidence for major clinical benefit, it is imperative that health systems evaluate new treatments to maximize the value of health care expenditures. This study evaluated healthcare costs among mBC patients treated with HER2-targeted therapy. Methods: A retrospective cohort study using the IQVIA Real-World Data Adjudicated Claims Database (1/1/2015-7/31/2019) was conducted. Adult (≥18-years) female patients who initiated HER2-targeted therapy with evidence of mBC diagnosis in the prior year were identified. The study index date was the initiation date of the HER2-targeted agent after which, patients were required to have ≥12 months of follow-up. Annual all-cause and BC-related healthcare costs per patient (2019 USD) were computed using payer-paid amounts in the first and second year following the index date. BC-related costs were defined as costs for claims with a primary diagnosis for BC (ICD-9-CM: 174.% or ICD-10-CM: C50.%) or BC-related treatment (surgery – mastectomy or lumpectomy, HER2-targeted therapy, chemotherapy, hormone therapy, immunotherapy, and radiation). Results: 708 mBC patients treated with HER2-targeted therapy were included with a mean age (SD) of 53.2 (10.2) years and mean follow-up of about 2 years. During the follow-up period, trastuzumab (96.5%) and pertuzumab (81.2%) were the most common HER2-targeted therapies used followed by ado-trastuzumab (15.4%), neratinib (6.3%), and lapatinib (5.3%). Additionally, patients received other treatments including chemotherapy (88.0%), hormone therapy (56.6%), and radiation therapy (57.6%). Of note, 40.3% of patients underwent surgery (mastectomy or lumpectomy) following evidence of metastasis. Following initiation of HER2-targeted therapy, mean annual costs per patient in Year 1 and Year 2 were $330,784 and$196,139, respectively. Correspondingly, BC-related costs in Year 1 and Year 2 were $255,273 and$144,978, respectively. HER2-targeted therapies accounted for 72% of BC-related costs in both Year 1 and 2. Surgery patients incurred $37,822 higher BC-related costs in Year 1 compared to non-surgery patients. However, in Year 2, the opposite was noted with non-surgery patients having$70,885 higher BC-related costs, mainly due to a differences in BC treatment rates in Year 2 for HER2 targeted drugs, other BC drugs and radiation. Conclusion: Total BC-related costs of mBC patients treated with HER2-targeted therapy is highest in the first year following treatment initiation, with the main cost driver being the cost of HER2-targeted therapy. While total costs decreased in the subsequent year, the cost of HER2 targeted therapy remained the dominant component. Results of this study highlight the significant economic burden of treating HER2+ mBC and also the need for therapies that limit disease progression. Page 1 of 1 Citation Format: Reshma Mahtani, Deepa Lalla, Nina Oestreicher, Augustina Ogbonnaya, Vishal Saundankar, Joanne Willey, Anna Coutinho, Kelly McCann. Healthcare costs for metastatic breast cancer patients treated with human epidermal growth factor receptor 2 targeted agents [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-54

Health Care Resource Utilization and Costs for Metastatic Breast Cancer Patients Newly Treated with Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Agents

HER2-positive metastatic breast cancer (mBC) is an incurable disease associated with years of chronic therapy and excess cost. HER2-targeted therapies have shown survival benefit for early-stage and mBC; however, the economic impact of these therapies has not been fully assessed. We evaluated health care resource use (HCRU) and costs of mBC patients treated with HER2-targeted therapy. This was a retrospective cohort study using the IQVIA Real-World Data Adjudicated Claims Database (July 1, 2014 to July 31, 2019). Female patients aged ≥18 years with mBC who initiated HER2-targeted therapy in the prior year were identified. The index date was the initiation date of the HER2-targeted agent, after which patients were required to have ≥12 months of follow-up. Annual and cumulative all-cause and BC-related costs (2019 USD) and annual BC-related HCRU were computed in years 1, 2, and 3 following the index date. Following the initiation of HER2-targeted therapy, the mean annual total all-cause costs per patient in years 1 (n = 423), 2 (n = 357), and 3 (n = 166) were $320,892 (SD:$224,343), $235,159 (SD:$185,287), and $226,254 (SD:$197,901), respectively. The mean annual total BC-related costs were $240,048 (SD:$151,230), $175,631 (SD:$148,058), and $165,506 (SD:$159,374) in years 1, 2, and 3, respectively. A major portion of BC-related costs were costs associated with HER2-targeted treatment. The 3-year cumulative all-cause and BC-related total costs were $769,573 (SD:$456,920) and $624,455 (SD:$401,319), respectively. Treatment of HER2-positive mBC is a substantial economic burden. A potential approach to minimizing cost and HCRU is to prevent recurrence

DOSE ADJUSTMENT PRACTICES OF PEGINESATIDE VS. EPOETIN IN EMERALD 1 AND 2 PIVOTAL TRIALS

Peginesatide (P) is a synthetic, pegylated, peptide-based ESA approved for treatment of anemia due to chronic kidney disease in adult patients (pts) on dialysis. P demonstrated noninferiority to epoetin (E) in maintenance of Hb levels in hemodialysis (HD) pts in two Phase 3 randomized, active-controlled, open-label trials (EMERALD 1,2). A large dialysis organization (LDO) recently reported an ESA dose adjustment rate of 12.1/pt-year (Bond et al, ISPOR 2012). This post hoc analysis evaluated dosing practices for maintaining Hb with P vs E. Pooled data from the two trials compared P (1x monthly; N=1066) with E (1-3x wkly; N=542) in HD pts previously on stable doses of E. Hb was measured during screening, at baseline and wkly (evaluation period, wks 29-36) or every 2 wks (all other periods). Dose adjustments were not to be made more frequently than every 4 wks, unless required for safety purposes. Dose adjustments (defined as change >±20% from last dose) were evaluated during the titration (wks 0-28), evaluation, and long-term follow-up (LT, wks 36-52) periods. Dose postponements were defined as >35d for P; for E, they were >4d, 6d, or 9d for TIW, BIW, and QW, respectively. Across the entire study period, P doses were adjusted ∼3 times less frequently and held ∼8 times less than P (Table). P (per pt-year) E (per pt-year) E/P ratio Total Dose Adjustments 3.5 10.3 2.9 Dose Increases 1.7 5.3 3.0 Dose Decreases 1.8 5.0 2.8 Dost Postponements 0.6 5.0 8.3 Within each treatment arm, dose adjustment and postponement rates (including corresponding E/P ratios) were similar across titration, evaluation, and LT periods. E dose adjustment rate was similar to that of real world practice in an LDO. E doses were adjusted and held more frequently than P despite similar protocol specifications for dose alteration and Hb maintenance

Real-World Evaluation of Patiromer for the Treatment of Hyperkalemia in Hemodialysis Patients

Introduction: Patiromer is a potassium (K+) binding polymer indicated for treating hyperkalemia. Among patients receiving chronic hemodialysis (HD), this study aimed to identify patient characteristics associated with patiromer initiation, describe patiromer utilization, and analyze serum K+ pre- and post-patiromer initiation. Methods: In a retrospective cohort study, using electronic health record data from a large dialysis provider in the United States (study period: December 21, 2015, to December 20, 2016), HD patients were included who had a medication order for patiromer, sodium polystyrene sulfonate (SPS), or laboratory evidence of hyperkalemia (no K+ binder [NoKb] cohort). The index date was the first order for patiromer/SPS, or the first K+ ≥5.0 mEq/l (NoKb cohort), respectively. Using multivariable logistic regression, we identified patient characteristics associated with patiromer initiation. We evaluated patiromer utilization using Kaplan-Meier methodology and proportion of days covered. Serum K+ concentrations were assessed pre- versus post-patiromer initiation. Results: Study cohorts included 527 (patiromer), 852 (SPS), and 8747 (NoKb) HD patients. Median follow-up was 141 days. Patiromer initiators were 2.6 times more likely to have had multiple prior episodes of hyperkalemia (odds ratio [OR]: 2.6; 95% confidence interval [CI]: 1.8–3.7). Most (61%) commenced patiromer on 8.4 g once daily; 60% of patients’ first patiromer order remained open after 180 days. Statistically significant reductions in K+, averaging approximately −0.5 mEq/l, were observed post-patiromer initiation (48% pre-patiromer vs. 22% post-patiromer had K+ ≥6.0 mEq/l [P < 0.001]). Conclusion: Patiromer initiators receiving chronic hemodialysis had comparatively more severe, uncontrolled baseline hyperkalemia. Medication order data show long-term patiromer use was associated with significantly reduced K+. Keywords: hemodialysis, hyperkalemia, patirome

Active, but not passive cigarette smoking was inversely associated with mammographic density

The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism. We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Women’s Health Across the Nation (SWAN). We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked ≥20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked ≥20 cigarettes/day was associated with 23.8% lower density, compared to having smoked ≤9 cigarettes/day (p &lt; 0.001). Our findings support the hypothesis that tobacco smoke exerts an antiestrogenic effect on breast tissue, but counters the known increased risk of breast cancer with smoking prior to first full-term birth. Thus, our data suggest that the antiestrogenic but not the carcinogenic effects of smoking may be reflected by breast density

Cost-Effectiveness Analysis of Patiromer and Spironolactone Therapy in Heart Failure Patients with Hyperkalemia.

Background and objectiveCertain patients with heart failure (HF) are unable to tolerate spironolactone therapy due to hyperkalemia. Patiromer is a novel agent used to treat hyperkalemia and has been shown to be efficacious, safe, and well-tolerated. The potential clinical outcomes and economic value of using patiromer and spironolactone in patients with HF unable to otherwise tolerate spironolactone due to hyperkalemia are unclear. The objective of this analysis was to model the potential pharmacoeconomic value of using patiromer and spironolactone in patients with a history of hyperkalemia that prevents them from utilizing spironolactone.MethodsWe performed a cost-effectiveness analysis of treatment with patiromer, spironolactone, and an angiotensin-converting enzyme inhibitor (ACEI) in patients with New York Heart Association (NYHA) class III-IV HF compared with ACEI alone. A Markov model was constructed to simulate a cohort of 65-year-old patients diagnosed with HF from the payer perspective across the lifetime horizon. Clinical inputs were derived from the RALES and OPAL-HK randomized trials of spironolactone and patiromer, respectively. Utility estimates and costs were derived from the literature and list prices. Outcomes assessed included hospitalization, life expectancy, and quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were performed to test the robustness of the model findings.ResultsTreatment with patiromer-spironolactone-ACEI was projected to increase longevity compared with ACEI alone (5.29 vs. 4.62 life-years gained, respectively), greater QALYs (2.79 vs. 2.60), and costs (US$28,200 vs. US$18,200), giving an ICER of US$52,700 per QALY gained. The ICERs ranged from US$40,000 to US$85,800 per QALY gained in 1-way sensitivity analyses.ConclusionOur results suggest that the use of spironolactone-patiromer-ACEI may provide clinical benefit and good economic value in patients with NYHA class III-IV HF unable to tolerate spironolactone due to hyperkalemia

Cost-Effectiveness Analysis of Patiromer and Spironolactone Therapy in Heart Failure Patients with Hyperkalemia.

Background and objectiveCertain patients with heart failure (HF) are unable to tolerate spironolactone therapy due to hyperkalemia. Patiromer is a novel agent used to treat hyperkalemia and has been shown to be efficacious, safe, and well-tolerated. The potential clinical outcomes and economic value of using patiromer and spironolactone in patients with HF unable to otherwise tolerate spironolactone due to hyperkalemia are unclear. The objective of this analysis was to model the potential pharmacoeconomic value of using patiromer and spironolactone in patients with a history of hyperkalemia that prevents them from utilizing spironolactone.MethodsWe performed a cost-effectiveness analysis of treatment with patiromer, spironolactone, and an angiotensin-converting enzyme inhibitor (ACEI) in patients with New York Heart Association (NYHA) class III-IV HF compared with ACEI alone. A Markov model was constructed to simulate a cohort of 65-year-old patients diagnosed with HF from the payer perspective across the lifetime horizon. Clinical inputs were derived from the RALES and OPAL-HK randomized trials of spironolactone and patiromer, respectively. Utility estimates and costs were derived from the literature and list prices. Outcomes assessed included hospitalization, life expectancy, and quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were performed to test the robustness of the model findings.ResultsTreatment with patiromer-spironolactone-ACEI was projected to increase longevity compared with ACEI alone (5.29 vs. 4.62 life-years gained, respectively), greater QALYs (2.79 vs. 2.60), and costs (US$28,200 vs. US$18,200), giving an ICER of US$52,700 per QALY gained. The ICERs ranged from US$40,000 to US$85,800 per QALY gained in 1-way sensitivity analyses.ConclusionOur results suggest that the use of spironolactone-patiromer-ACEI may provide clinical benefit and good economic value in patients with NYHA class III-IV HF unable to tolerate spironolactone due to hyperkalemia