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Purpose: Clinical outcomes have improved for women with early stage, HER2-positive breast cancer following the FDA approval of adjuvant trastuzumab use in 2006. However, only limited information exists on such patients' outcomes in real-world settings outside of clinical trials. We examined the risk of subsequent breast cancer in women with HER-2 positive disease, and the impact of trastuzumab use, in a large California community-based health plan. Patients and Methods: A cohort of 3550 women with HER2-positive breast cancer (stages I-III) from 2009-2017 were followed through December 2018. We calculated subsequent breast cancer (SBC) rates overall and by trastuzumab use. Multivariable Cox proportional hazards modeling was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for SBC by trastuzumab use. Results: Within the cohort diagnosed with HER2-positive disease, 81% received adjuvant trastuzumab. After 4.1 mean years follow-up (maximum 10 years), the risk of SBC was 22% lower with adjuvant trastuzumab use (hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.66-0.92) compared with non-use. The cumulative incidence of SBC precipitously rose two years after diagnosis and by the 10th year, the cumulative incidence was 31% among those who had trastuzumab therapy versus 34% without this therapy. Conclusion: In community practice settings, the cumulative incidence of SBC in patients with early stage HER2-positive BC was 31% at 10 years in a cohort treated with adjuvant trastuzumab. Trastuzumab use was associated with a 22% reduced risk of developing SBC. This residual disease burden suggests breast cancer outcomes may be improved with further treatment given the advent of next-generation HER2-targeted therapies.
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BACKGROUND: Approximately half of patients with high-risk HER2-positive early-stage breast cancer (ESBC) do not have pathologic complete response (pCR) after neoadjuvant therapy. The residual burden of disease among this population has not been previously quantified. MATERIALS AND METHODS: We used decision-modeling techniques to simulate recurrence, progression from locoregional to distant cancer, breast cancer-related mortality, and mortality from other causes over a 10-year period in a hypothetical cohort. We derived progression probabilities primarily from the KATHERINE trial of T-DM1 (ado-trastuzumab emtansine) and mortality outcomes from the published literature. Modeled outcomes included recurrences, breast cancer deaths, deaths from other causes, direct medical costs, and costs due to lost productivity. To estimate the residual disease burden, we compared outcomes from a cohort of patients treated with T-DM1 versus a hypothetical cohort with no disease recurrence. RESULTS: We estimated that 9,300 people would experience incident high-risk HER2-positive ESBC in the United States in 2021 based on cancer surveillance databases, clinical trial data, and expert opinion. We estimated that, in this group, 2,118 would experience disease recurrence, including 1,576 distant recurrences, and 1,358 would experience breast cancer deaths. This residual disease burden resulted in 6,435 life-years lost versus the recurrence-free cohort, and healthcare-related costs totaling $644 million, primarily associated with treating distant cancers. CONCLUSION: Patients with HER2-positive ESBC who do not achieve pCR after neoadjuvant therapy are at ongoing risk of recurrence despite the effectiveness of neoadjuvant treatment. There is substantial clinical and economic value in further reducing the residual disease burden in this population.
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Neoplasias de la Mama , Terapia Neoadyuvante , Humanos , Estados Unidos/epidemiología , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Trastuzumab/uso terapéutico , Receptor ErbB-2 , Recurrencia Local de Neoplasia/tratamiento farmacológico , Ado-Trastuzumab Emtansina/uso terapéutico , Neoplasia Residual/tratamiento farmacológico , Progresión de la Enfermedad , Costo de EnfermedadRESUMEN
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Treatment of HER2-positive mBC is a substantial economic burden. A potential approach to minimizing cost and HCRU is to prevent recurrence.
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Antineoplásicos , Neoplasias de la Mama , Adolescente , Adulto , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/patología , Femenino , Humanos , Aceptación de la Atención de Salud , Receptor ErbB-2/metabolismo , Estudios RetrospectivosAsunto(s)
Diagnóstico Tardío , Fibrosis Pulmonar Idiopática/diagnóstico , Medicare/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Fibrosis Pulmonar Idiopática/epidemiología , Incidencia , Masculino , Prevalencia , Pruebas de Función Respiratoria/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Estados Unidos/epidemiologíaRESUMEN
Background The Phase IIIb, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS) trial will assess r-tPA in ischemic stroke patients who present with mild deficits (i.e. mild stroke). Aims To assess PRISMS's societal value in clarifying the optimal care for patients with mild ischemic stroke. Methods A value of information (VOI) decision model was developed to compare the outcomes of mild stroke patients treated vs. not treated with r-tPA. Model inputs were derived from a subset of Third International Stroke Trial patients, a recent meta-analysis of r-tPA trials, expert opinion, and other published sources. VOI analyses were also used to assess the expected US societal value of the PRISMS trial and the expected value of reducing uncertainty in key trial estimates. Results The expected net societal value of the PRISMS trial was approximately $210 million ($160 m-$260 m), representing a six-fold return on investment. The value of reducing uncertainty in r-tPA efficacy was approximately $150 million ($100 m-$200 m), while reducing uncertainty in r-tPA safety (increased risk for symptomatic intracranial hemorrhage) did not add additional value in comparison. Conclusions Developing a better understanding of the outcomes of r-tPA treatment in patients with mild ischemic stroke will provide tremendous societal value by clarifying current uncertainty around treatment effectiveness. Enrollment in the PRISMS trial for patients presenting with mild ischemic stroke within 0-3 h of symptom onset should be highly encouraged.
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Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Análisis Costo-Beneficio , Método Doble Ciego , Fibrinolíticos/efectos adversos , Humanos , Modelos Teóricos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Factores de Tiempo , Tiempo de Tratamiento , Activador de Tejido Plasminógeno/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Intravenous recombinant tissue-type plasminogen activator (r-tPA) is an approved treatment for select patients with acute ischemic stroke (AIS). Data indicate r-tPA improves functional outcome three months after AIS compared with placebo. This study models the increase in quality adjusted life years (QALYs) associated with r-tPA compared with similar patients not treated with r-tPA. METHODS: Hospital discharge data for AIS and r-tPA were obtained from the Nationwide Inpatient Sample from 1998 to 2011. Discharge location (home, rehabilitation, long-term care, death) was mapped to modified Rankin Scale (mRS) scores based on National Institute of Neurological Disorders and Stroke (NINDS) Study Group Part 1 and 2 clinical studies. The mRS scores were mapped to relative risk of death and QALYs obtained from the literature. The model estimated expected survival and QALYs by age, gender and mRS for patients receiving r-tPA. Life expectancy and QALYs for patients not receiving r-tPA were estimated based on discharge location and mRS for placebo patients in the NINDS study. RESULTS: AIS discharges declined from over 635,000 in 1998 to over 593,000 in 2011. A total of 183,235 patients received r-tPA. Utilization of r-tPA increased from 1% of AIS patients in 1998 to over 4% in 2011. Estimated projections for QALYs gained from utilization of r-tPA to QALYS without r-tPA were just under 240,000 for the 13 years and with no discounting, and just over 165,000 assuming 3% annual discounting. In the most conservative scenario, assuming no difference in proportional discharge status (i.e. patients not treated with r-tPA are discharged in the same manner as r-tPA patients), the estimated life years gained are approximately 35,000 and QALYS gained are approximately 90,000. CONCLUSIONS: r-tPA for AIS has resulted in estimated gains in quality-adjusted life years due to reduction in disability and improvement in functioning since its introduction in 1998.
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Años de Vida Ajustados por Calidad de Vida , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Administración Intravenosa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Utilización de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/tendencias , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Método de Montecarlo , Alta del Paciente/estadística & datos numéricos , Alta del Paciente/tendencias , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Índice de Severidad de la Enfermedad , Activador de Tejido Plasminógeno/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: HER2 positive (HER2+) metastatic breast cancer (MBC) is associated with high mortality. Trastuzumab was approved for use in 1998, but the life-years saved from first-line use are unknown, as are the potential US population benefits from adding pertuzumab. OBJECTIVES: The first aim was to estimate the number of life-years saved by using first-line trastuzumab between 1999 and 2013 in HER2+ women with MBC. In addition, based on these estimates, the second aim was to project the life-years that could be saved by adding pertuzumab to trastuzumab in first-line therapy. METHODS: We constructed a simulation model accounting for incidence, testing rates, therapy utilization, and overall survival. The model was run for 1999 to 2013 (15 years) to estimate the life-years saved from using trastuzumab plus chemotherapy instead of chemotherapy alone. The model was also run from 2013 to 2027 (15 years) to project the life-years that might be saved by adding pertuzumab. Uncertainty was incorporated using Monte-Carlo methods. RESULTS: The estimated number of women with HER2+ MBC varied over time, with the peak of 9700 in 2005 and the low of 7700 in 2018. The cumulative incremental life-years saved because of first-line trastuzumab use from 1999 to 2013 was estimated to be 156,413 (95% simulation interval 114,840-195,201). The projection for pertuzumab from 2013 to 2027 was 137,959 (95% simulation interval 56,011-225,069). Exploratory analyses of value showed that pertuzumab, trastuzumab, and chemotherapy is associated with a $1.10 billion gain compared with chemotherapy alone, and adding pertuzumab is associated with a $0.06 billion gain compared with trastuzumab with chemotherapy. CONCLUSIONS: This simulation model suggests that substantial progress has been made in treating HER2+ women over the past 15 years, and the future may witness similar gains with the introduction of pertuzumab.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/antagonistas & inhibidores , Neoplasias de la Mama/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor ErbB-2/antagonistas & inhibidores , Trastuzumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/economía , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/economía , Neoplasias de la Mama/mortalidad , Simulación por Computador , Análisis Costo-Beneficio , Costos de los Medicamentos , Femenino , Investigación sobre Servicios de Salud , Humanos , Incidencia , Estimación de Kaplan-Meier , Modelos Económicos , Modelos Estadísticos , Terapia Molecular Dirigida , Método de Montecarlo , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/economía , Años de Vida Ajustados por Calidad de Vida , Receptor ErbB-2/análisis , Factores de Tiempo , Trastuzumab/efectos adversos , Trastuzumab/economía , Resultado del Tratamiento , Incertidumbre , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Patients with breast cancer whose tumors test positive for human epidermal growth factor receptor 2 (HER2) are treated with HER2-targeted therapies such as trastuzumab, but limitations with HER2 testing may lead to false-positive (FP) or false-negative (FN) results. OBJECTIVES: To develop a US-level model to estimate the effect of tumor misclassification on health care costs and patient quality-adjusted life-years (QALYs). METHODS: Decision analysis was used to estimate the number of patients with early-stage breast cancer (EBC) whose HER2 status was misclassified in 2012. FP results were assumed to generate unnecessary trastuzumab costs and unnecessary cases of trastuzumab-related cardiotoxicity. FN results were assumed to save money on trastuzumab, but with a loss of QALYs and greater risk of disease recurrence and its associated costs. QALYs were valued at $100,000 under a net monetary benefit approach. RESULTS: Among 226,870 women diagnosed with EBC in 2012, 3.12% (n = 7,070) and 2.18% (n = 4,955) were estimated to have had FP and FN test results, respectively. Approximately 8400 QALYs (discounted, lifetime) were lost among women not receiving trastuzumab because of FN results. The estimated incremental per-patient lifetime burden of FP or FN results was $58,900 and $116,000, respectively. The implied incremental losses to society were $417 million and $575 million, respectively. CONCLUSIONS: HER2 tests result in misclassification and nonoptimal treatment of approximately 12,025 US patients with EBC annually. The total economic societal loss of nearly $1 billion suggests that improvements in HER2 testing accuracy are needed and that further clinical and economic studies are warranted.
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Neoplasias de la Mama/economía , Neoplasias de la Mama/genética , Costo de Enfermedad , Pruebas Genéticas/economía , Receptor ErbB-2/genética , Neoplasias de la Mama/diagnóstico , Técnicas de Apoyo para la Decisión , Diagnóstico Precoz , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Pruebas Genéticas/normas , Pruebas Genéticas/tendencias , Humanos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: Despite the availability of results from multiple newer clinical trials and changing healthcare costs, the cost-effectiveness of recombinant tissue-type plasminogen activator (r-tPA) for treatment of acute ischemic stroke within 0 to 3 hours of symptom onset was last evaluated in 1998 for the United States Using current evidence, we evaluate the long-term cost-effectiveness of r-tPA administered 0 to 3 hours after acute ischemic stroke onset versus no r-tPA. METHODS: A disease-based decision model to project lifetime outcomes of patients after acute ischemic stroke by r-tPA treatment status from the US payer perspective was developed. Model inputs were derived from a recent meta-analysis of r-tPA trials, cohort studies, and health state preference studies. Cost data, inflated to 2013 dollars, were based on drug wholesale acquisition cost and the literature. To compare r-tPA to no r-tPA, we calculated incremental total direct costs, incremental quality-adjusted life years, and incremental cost-effectiveness ratios. We performed 1-way and probabilistic sensitivity analyses to evaluate uncertainty in the results. RESULTS: r-tPA resulted in a gain of 0.39 quality-adjusted life years (95% confidence range, 0.16-0.66) on average per patient and a lifetime cost-saving of $25,000 (95% confidence range, -$42,500 to -$11,000) compared with no r-tPA. In probabilistic sensitivity analyses, r-tPA was dominant compared with no r-tPA in ≈100% of simulations. The model was sensitive to inputs for r-tPA efficacy, healthcare costs for disabled patients, mortality rates for disabled and nondisabled patients, and quality of life estimates. CONCLUSIONS: Our analysis supports earlier economic evaluations that r-tPA is a cost-effective method to treat stroke. Appropriate use of r-tPA should be prioritized nationally.
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Fibrinolíticos/economía , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/economía , Activador de Tejido Plasminógeno/uso terapéutico , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Humanos , Años de Vida Ajustados por Calidad de Vida , Estados UnidosRESUMEN
BACKGROUND: Existing treatments for metastatic breast cancer (mBC) are often effective but can cause adverse events (AEs). This study aimed to identify AEs associated with chemotherapies commonly used in mBC treatment (phase 1) and to quantify the economic impact of these AEs (phase 2). MATERIALS AND METHODS: Patients in phase 1 had at least one claim for therapy for mBC, with at least one episode with single or multiple agents. The most common chemotherapy-related complications were identified using medical and pharmacy claims data. In phase 2, patients meeting study criteria were divided into four treatment cohorts by the line of treatment and chemotherapy received: first-line taxane-treated patients, second-line taxane-treated patients, first-line capecitabine-treated patients, and second-line capecitabine-treated patients. Average monthly AE-related health care costs per cohort were stratified by cost component. Total monthly costs per number of AEs were also calculated. RESULTS: On average, patients in phase 1 (n = 1,551) had 2 episodes of treatment, with a mean duration of 131 days. The most frequently noted complications were anemia (50.7% of mBC treatment episodes), bilirubin elevation (26.4%), and leukopenia (24.8%). In phase 2, costs related to AEs were primarily driven by incremental inpatient, outpatient, and pharmacy costs. Increases in average monthly costs ranged from $854 (9.0%) to $5,320 (69.5%), according to cohort. Overall costs increased with increasing numbers of AEs. CONCLUSION: Chemotherapy-related AEs in patients with mBC are associated with a substantial economic burden that increases with the number of AEs reported.
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Neoplasias de la Mama/economía , Costos y Análisis de Costo/economía , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/economía , Costos de la Atención en Salud , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Hidrocarburos Aromáticos con Puentes/economía , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Capecitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/economía , Desoxicitidina/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Fluorouracilo/análogos & derivados , Fluorouracilo/economía , Fluorouracilo/uso terapéutico , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Taxoides/economía , Taxoides/uso terapéuticoRESUMEN
PURPOSE: We sought to compare the economic impact of treatment-related adverse events (AEs) in patients with metastatic breast cancer (mBC) using taxane- or capecitabine-based treatment regimens as either first- or second-line (FL or SL) therapy in the US. METHODS: We used healthcare claims data from the Truven Health Analytics MarketScan® Commercial Databases to conduct a retrospective cohort study comparing the economic impact of AEs amongst taxane- and capecitabine-treated mBC patients in the US. We selected women diagnosed with mBC between 2008-2010 who received a taxane or capecitabine as first- or second-line (FL or SL) chemotherapy. Costs related to hospitalization, outpatient services, emergency department visits, chemotherapy and other medications were tabulated and combined to determine total healthcare costs. The incremental monthly costs associated with the presence of AEs compared to no AEs were estimated using generalized linear models, controlling for age and Charlson Comorbidity Index. RESULTS: We identified 15,443 mBC patients meeting inclusion criteria. Adjusted total monthly costs were significantly higher in those who experienced AEs than in those without AEs in both lines of treatment (FL incremental cost: taxanes $1,142, capecitabine $1,817; SL incremental cost: taxanes $1,448, capecitabine $4,437). Total costs increased with the number of AEs and were primarily driven by increased hospitalization amongst those with AEs. CONCLUSIONS: Adverse events in taxane- or capecitabine-treated mBC patients are associated with significant increases in costs. Selecting treatment options associated with fewer AEs may reduce costs and improve outcomes in these patients.
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Few studies have compared treatment patterns, healthcare resource utilization (HRU), and costs in patients with metastatic breast cancer (mBC) receiving HER2 directed therapy. This study evaluated these outcomes in patients receiving trastuzumab or lapatinib. Adult women with mBC, who were initiated on trastuzumab or lapatinib, on or after March 13, 2007, were selected from the US-based PharMetrics® Integrated Database (2000-2011). Patients were required to be continuously enrolled in their healthcare plan for ≥6 months prior to and ≥30 days following trastuzumab or lapatinib initiation. Trastuzumab or lapatinib discontinuation rates (defined as a gap ≥45 consecutive days) were compared using multivariate Cox proportional-hazards models. HRU and monthly healthcare cost differences were estimated using multivariate negative binomial regression models and generalized linear models, respectively. Among the 643 patients who met the inclusion criteria, 381 and 262 patients were included in the trastuzumab and lapatinib groups, respectively. The majority of the 262 patients receiving lapatinib previously received trastuzumab (N = 171 [65.3%]). After adjustment for potential confounders, when compared to trastuzumab patients, lapatinib patients had a higher rate of treatment discontinuation (hazard ratio [HR] = 1.57; P < 0.001), a higher rate of outpatient visits (not treatment administration related) (IRR = 1.19; P < 0.004), and a lower rate of medical visits associated with treatment administration (IRR = 0.34; P < 0.001). There were no significant differences between the two groups in total monthly healthcare costs ($11,920 vs. $11,898 for trastuzumab and lapatinib patients, respectively; P = 0.451). Findings from our study show that, irrespective of the treatment initiated at index date, disease management in patients with mBC is associated with similar and substantial healthcare costs. Any differences in specific components of healthcare costs were associated with differences in the mode of treatment administration. Approximately 50% of all costs were non-drug related, and future studies should focus on how these costs may be controlled, regardless of mode of treatment administration.
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BACKGROUND: The importance of human epidermal growth factor receptor 2 (HER2) as a prognostic and predictive marker in invasive breast cancer is well established. Accurate assessment of HER2 status is essential to determine optimal treatment options. METHODS: Breast cancer tumor tissue samples from the VIRGO observational cohort tissue substudy that were locally HER2-negative were retested centrally with both US Food and Drug Administration (FDA)-approved immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, using FDA-approved assay cutoffs; results were compared. RESULTS: Of the 552 unique patient samples centrally retested with local HER2-negative results recorded, tumor samples from 22 (4.0%) patients were determined to be HER2-positive (95% confidence interval [CI] = 2.5%-5.7%). Of these, 18 had been tested locally by only one testing methodology; 15 of 18 were HER2-positive after the central retesting, based on the testing methodology not performed locally. Compared with the 530 patients with centrally confirmed HER2-negative tumors, the 22 patients with centrally determined HER2-positive tumors were younger (median age 56.5 versus 60.0 years) and more likely to have ER/PR-negative tumors (27.3% versus 22.3%). These patients also had shorter median progression-free survival (6.4 months [95% CI = 3.8-15.9 months] versus 9.1 months [95% CI = 8.3-10.3 months]) and overall survival (25.9 months [95% CI = 13.8-not estimable] versus 27.9 months [95% CI = 25.0-32.9 months]). CONCLUSIONS: This study highlights the limitations of employing just one HER2 testing methodology in current clinical practice. It identifies a cohort of patients who did not receive potentially efficacious therapy because their tumor HER2-positivity was not determined by the test initially used. Because of inherent limitations in testing methodologies, it is inadvisable to rely on a single test to rule out potential benefit from HER2-targeted therapy.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Reacciones Falso Negativas , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Estudios Prospectivos , Receptor ErbB-2/genética , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Adjuvant trastuzumab treatment is administered to early stage breast cancer patients in physician office (POV) or hospital outpatient (HOP) settings. OBJECTIVE: To identify treatment patterns, utilization, and costs by site of care (POV vs. HOP) of patients with adjuvant treatment of breast cancer with trastuzumab. METHODS: This retrospective analysis identified adult, female breast cancer patients who initiated trastuzumab treatment (index date) from a large U.S. claims database. Inclusion criteria also required ≥ 2 claims for both trastuzumab (from July 1, 2006, to July 31, 2012) and breast cancer (during 6-month pre-index baseline period), no evidence of metastatic breast cancer or other cancers in the baseline period, and continuous enrollment with commercial or Medicare Advantage coverage 6 months pre- and post-index, except that patients who died during follow-up were retained. Patients with evidence of trastuzumab receipt during the baseline period or more than 1 site of care during follow-up were excluded. Patients were stratified by site of care and were followed from index date to 30 days after the last trastuzumab infusion prior to a gap ≥ 90 days, death, disenrollment, or end-of-study period. Differences in treatment patterns between the POV and HOP cohorts were assessed by t-test and chi-square test. The relationship between site of care and health care costs was modeled with a generalized linear model with gamma distribution and log link, and the number of trastuzumab infusions was modeled with negative binomial regression controlling for log follow-up time. All models were adjusted for age, baseline comorbidity score, and insurance type. RESULTS: Of the 3,439 breast cancer patients identified, 77.6% (2,669) received adjuvant trastuzumab in the POV setting. Mean age (53.7 years) and baseline comorbidity score (3.91) were similar among cohorts; a higher percentage of POV versus HOP patients had commercial insurance (91.1% vs. 86.4%, P < 0.001). Compared with the POV cohort, HOP patients had a shorter mean duration of trastuzumab treatment (324.8 vs. 343.0 days, P < 0.001); more treatment gaps (30-59 day gap: 67.4% vs. 24.1%, P < 0.001); and fewer trastuzumab infusions per month (1.37 vs. 1.98, P < 0.001) during follow-up. In multivariate analysis, the monthly count of trastuzumab infusions in the HOP cohort was lower than the POV cohort (incidence rate ratio = 0.693; 95% CI = 0.672-0.715). Adjusted per patient per month total health care costs were 53.6 % higher in the HOP setting (cost ratio = 1.536, 95% CI = 1.472-1.604). CONCLUSIONS: Breast cancer patients treated with adjuvant trastuzumab in the HOP setting had a shorter duration of trastuzumab treatment and fewer trastuzumab infusions but incurred higher monthly total costs than patients treated in the POV setting.
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Atención Ambulatoria/economía , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/economía , Antineoplásicos/administración & dosificación , Antineoplásicos/economía , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/economía , Costos de los Medicamentos , Recursos en Salud/economía , Visita a Consultorio Médico/economía , Servicio Ambulatorio en Hospital/economía , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Esquema de Medicación , Revisión de la Utilización de Medicamentos , Femenino , Recursos en Salud/estadística & datos numéricos , Humanos , Modelos Lineales , Programas Controlados de Atención en Salud , Persona de Mediana Edad , Modelos Económicos , Análisis Multivariante , Estadificación de Neoplasias , Pautas de la Práctica en Medicina/economía , Estudios Retrospectivos , Factores de Tiempo , Trastuzumab , Estados UnidosRESUMEN
Treatment options for metastatic breast cancer (MBC) are complex, and some patients experience early discontinuation or switching of treatment (ETDS). We examined the relationship between ETDS and patient-reported symptom burden among patients receiving first-line treatment of MBC in community oncology settings. This retrospective observational study used the ACORN Data Warehouse, a comprehensive community oncology repository of medical records and patient-reported outcomes. Patients with first-line treatment for MBC who had Patient Care Monitor (PCM) surveys were eligible. ETDS was defined as: record stating ETDS, treatment duration < planned, and planned therapy <6 weeks. Symptom burden was measured by two PCM composite scores [continuous (0-22) and categorical (absent, mild, moderate, and severe)] computed from 22 PCM items with varying cut points to assess symptom burden over time. Cox regression with time-varying covariates was used to assess risk for ETDS controlling for patient characteristics and treatment type: chemo (chemotherapy without targeted therapy (±hormone therapy); targeted (chemotherapy plus targeted therapy (±hormone therapy); and hormone (hormone therapy only). Overall, 197 (24.7 %) of a total sample of 797 patients had an ETDS event, of which 109 (55.3 %) were switches rather than early discontinuation. ETDS rate was nominally lower in the hormone group (11.1 %) versus chemo (27.6 %) or targeted (26.1 %). PCM continuous composite score predicted ETDS, controlling for other variables (HR = 1.132, p < 0.0001). ETDS was predicted by moderate and severe levels of PCM categorical composite score (HR = 4.135, and HR = 5.287 vs. absent, respectively, both p < 0.0001), with the pattern suggesting a threshold effect. Moderate or severe levels of a wide range of patient-reported symptoms and the accumulation of symptoms over time significantly predicted ETDS. Providers may better maintain patients on planned therapy if they attend to overall symptom burden patients experience over time.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Sustitución de Medicamentos , Privación de Tratamiento , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer. METHODS: A secondary endpoint of the EMILIA study was time to symptom worsening (time from randomization to the first documentation of a ≥ 5-point decrease from baseline) as measured by the Trial Outcome Index Physical/Functional/Breast (TOI-PFB) subset of the Functional Assessment of Cancer Therapy-Breast questionnaire. Predefined exploratory patient-reported outcome endpoints included proportion of patients with a clinically significant improvement in symptoms (per TOI-PFB) and proportion of patients with diarrhea symptoms (per Diarrhea Assessment Scale). RESULTS: In the T-DM1 arm, 450 of 495 patients had a baseline and ≥ 1 postbaseline TOI-PFB score versus 445 of 496 patients in the capecitabine-plus-lapatinib arm. Time to symptom worsening was delayed in the T-DM1 arm versus the capecitabine-plus-lapatinib arm (7.1 months versus 4.6 months, respectively; hazard ratio = 0.796; P = .0121). In the T-DM1 arm, 55.3% of patients developed clinically significant improvement in symptoms from baseline versus 49.4% in the capecitabine-plus-lapatinib arm (P = .0842). Although similar at baseline, the number of patients reporting diarrhea symptoms increased 1.5- to 2-fold during treatment with capecitabine and lapatinib but remained near baseline levels in the T-DM1 arm. CONCLUSIONS: Together with the EMILIA primary data, these results support the concept that T-DM1 has greater efficacy and tolerability than capecitabine plus lapatinib, which may translate into improvements in health-related quality of life.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/análisis , Ado-Trastuzumab Emtansina , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Estado de Salud , Humanos , Lapatinib , Maitansina/administración & dosificación , Maitansina/análogos & derivados , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Calidad de Vida , Quinazolinas/administración & dosificación , Autoinforme , Encuestas y Cuestionarios , Factores de Tiempo , Trastuzumab , Resultado del TratamientoRESUMEN
PURPOSE: Metastatic breast cancer (MBC) patients are treated with a variety of regimens with differing side effects that can reduce the patients' quality of life. This study assessed the willingness to pay (WTP) to avoid side effects related to MBC treatment using conjoint analysis. METHODS: An online, self-administered conjoint analysis survey of US adult female MBC patients was conducted to elicit preferences for MBC treatment side effects. Attributes included in the analysis were hair loss, diarrhea, fatigue, nausea, tingling in hands and feet, pain, risk of infection, and out-of-pocket costs. Fifteen choice-based conjoint questions were presented where patients selected the most preferred therapy. A partial profile design was used to allow for each treatment description to be made with 3 instead of all 8 attributes. The attribute choices for each question included 2 side effects and a yearly out-of-pocket price. RESULTS: There were 298 respondents. MBC patients were willing to pay (US$) $3,894 to avoid severe diarrhea, $3,479 to avoid being hospitalized due to infection, $3,211 to avoid severe nausea, $2,764 to avoid severe tingling in hands and feet, $2,652 to avoid severe fatigue, $1,853 to avoid obvious hair loss, and $1,458 to avoid severe pain. The most important attributes when selecting a therapy for MBC in terms of average utility were risk of infection, diarrhea, and nausea. CONCLUSIONS: MBC patients were willing to pay significant amounts to avoid side effects associated with MBC treatment, with patients willing to pay the most to avoid diarrhea, risk of infection, and nausea.
RESUMEN
While overall survival (OS) has historically been the primary endpoint for clinical trials in oncology, progression-free survival (PFS) has gained acceptance as a valuable surrogate endpoint. However, there are no known published reports about the value of PFS from the patient's perspective. We developed a questionnaire that included items regarding quality of life (QoL) and the importance of different treatment outcomes and presented hypothetical scenarios for which respondents were asked to indicate their preferences concerning treatments as they relate to PFS. 282 women with metastatic breast cancer (MBC), ranging in age from 21 to 80 years completed an online version of this questionnaire. The majority of women (66 %) had been diagnosed with MBC within the previous 3 years and 56 % had been told their MBC had progressed. When asked to rank five treatment characteristics from most important to least important, respondents ranked "extending PFS" as the second most important treatment outcome after OS. When presented with a hypothetical scenario of two women receiving different treatments, respondents preferred the treatment that resulted in longer PFS (16 vs. 12 months), even when OS and side effects were assumed to be equal. Specifically, when asked to consider which woman within the hypothetical scenario had better QoL, physical functioning, and emotional well-being, respondents more often chose the woman who experienced longer PFS (QoL: 40 vs. 6 %; physical functioning: 32 vs. 8 %; emotional well-being: 58 vs. 6 %) compared to the woman within the hypothetical scenario who had a shorter time of progression. Respondents rated their own QoL highest after being told their MBC was responding to treatment (mean score 76.6) versus after the initial diagnosis of breast cancer and MBC (68.5 and 60.3). These findings suggest that extending PFS is an important treatment outcome and, from a patient perspective, improves overall QoL, physical functioning, and emotional well-being.
Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/psicología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Evaluación del Resultado de la Atención al Paciente , Calidad de Vida , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: This study aims to describe and compare health-related quality of life (HRQL) in patients with node-positive and high-risk node-negative HER2-positive early breast cancer receiving adjuvant docetaxel and trastuzumab-based or docetaxel-based regimens alone. METHODS: Eligible patients (n = 3,222) were randomly assigned to either four cycles of adjuvant doxorubicin and cyclophosphamide followed by four cycles of docetaxel (ACâT) or one of two trastuzumab-containing regimens: adjuvant doxorubicin and cyclophosphamide followed by docetaxel plus trastuzumab administered for 1 year (ACâTH) or six cycles of docetaxel plus carboplatin combined with trastuzumab administered for 1 year (TCH). The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and BR-23 were administered at baseline, the start of cycle 4 (mid), and the end of chemotherapy (EOC), as well as at 6, 12, and 24 months after chemotherapy. RESULTS: Compliance rates for the EORTC questionnaires were acceptable at 72%-93% of eligible patients out to the 12-month assessment. Systemic side effect (SE) change scores were significantly improved for TCH-treated patients compared with ACâTH and ACâT at EOC, suggesting improved tolerability. Physical functioning (PF) was only slightly worse at midpoint for those receiving TCH, compared with patients who were just starting on taxane in an ACâTH regimen, but was otherwise similar between arms. All treatment arms recovered from the deterioration in SE, PF, and Global Health Scale scores by 1 year and median future perspective change scores continued to improve throughout treatment and follow-up. CONCLUSION: HRQL outcomes for adjuvant docetaxel and trastuzumab-based regimens are favorable and support TCH as a more tolerable treatment option.