Systematic literature review of clinical trials of endocrine therapies for premenopausal women with metastatic HR+ HER2- breast cancer.

Several endocrine-based therapies have recently been evaluated as treatments for premenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC). We conducted a systematic review and assessed the feasibility of an indirect treatment comparison (ITC) to characterize the comparative efficacy of endocrine-based therapies in this setting. A systematic literature review (SLR) of Medline, EMBASE, Cochrane Library and key conferences was performed to identify randomized clinical trials (RCTs) satisfying the following criteria: (a) included pre/perimenopausal women with HR+/HER2- mBC, (b) included endocrine-based therapies, (c) reported efficacy, safety, or quality of life outcomes, and (d) was published in 2007 or later (when HER2 testing was standardized). The clinical and methodological similarities across trials were assessed to evaluate the feasibility of an ITC. Four RCTs (PALOMA-3, MONARCH-2, KCSG BR10-04 and MONALEESA-7) and eight regimens (palbociclib + fulvestrant + goserelin, fulvestrant + goserelin, abemaciclib + fulvestrant + gonadotropin-releasing hormone agonist [GnRHa], fulvestrant + GnRHa, anastrozole + goserelin, goserelin, ribociclib + NSAI/tamoxifen + goserelin and NSAI/tamoxifen + goserelin) were selected. MONALEESA-7 was the only phase 3 trial investigating endocrine-based therapies as first-line in only pre/perimenopausal women with HR+/HER2- mBC; the other three trials focused on the ET-failure setting and their pre/perimenopausal populations were relatively small. ITCs were methodologically unfeasible due to critical differences in treatment settings and lack of common comparators across trials. Therefore, we were not able to characterize the relative efficacy of the different endocrine-based therapies available in the premenopausal HR+/HER2- mBC setting. This systematic review provides a comprehensive assessment of the available trial evidence on the efficacy and safety of endocrine-based therapies for premenopausal women with HR+/HER2- mBC. Only four trials have reported relevant data in this setting, and MONALEESA-7 is currently the only trial focused on premenopausal HR+ HER2- mBC in the first-line setting.

Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with ribociclib + letrozole: results from MONALEESA-2.

PURPOSE: Evaluate patient-reported outcomes (PROs) for postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer treated with first-line ribociclib plus letrozole. METHODS: In the phase III MONALEESA-2 study (NCT01958021), 668 patients were randomized 1:1 to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole. PROs were assessed using the European Organisation for Research and Treatment of Cancer core quality-of-life (EORTC QLQ-C30) and breast cancer-specific (EORTC QLQ-BR23) questionnaires. Changes from baseline and time to deterioration in health-related quality of life (HRQoL) were analyzed using linear mixed-effect and stratified Cox regression models, respectively. Exploratory analysis of area-under-the-curve for change from baseline in pain score (AUC-pain) was performed. RESULTS: On-treatment HRQoL scores were consistently maintained from baseline and were similar between arms. A clinically meaningful (> 5 points) reduction in pain score was observed as early as Week 8 and was maintained up to Cycle 15 in the ribociclib arm. A statistically significant increase in mean AUC-pain was also observed in the ribociclib arm. Scores for all other EORTC QLQ-C30 and EORTC QLQ-BR23 domains were maintained from baseline and were similar between arms. CONCLUSIONS: HRQoL was consistently maintained from baseline in postmenopausal women with HR+, HER2- advanced breast cancer receiving ribociclib plus letrozole and was similar to that observed in the placebo plus letrozole arm. Together with the improved clinical efficacy and manageable safety profile, these PRO results provide additional support for the benefit of ribociclib plus letrozole in this patient population.

Acute and chronic systemic corticosteroid-related complications in patients with severe asthma.

BACKGROUND: Many patients with severe asthma require maintenance treatment with systemic corticosteroids (SCSs) to control daily symptoms and prevent serious acute exacerbations, but chronic SCS use is associated with complications. OBJECTIVE: We sought to evaluate the risk of SCS-related complications by SCS exposure and quantify the associated health care costs and resource use in patients with severe asthma. METHODS: We performed a longitudinal, open-cohort, observational study using health insurance claims data (1997-2013: Medicaid) from Florida, Iowa, Kansas, Missouri, Mississippi, and New Jersey. Eligible patients were 12 years old or older with 2 or more asthma diagnoses and had more than 6 months of continuous SCS use. An open-cohort approach was used to classify patients' follow-up into low, medium, and high SCS exposure (≤ 6, >6-12, and >12 mg/d, respectively). Multivariate generalized estimating equation models were used to estimate the adjusted risk of SCS-related complications for patients with medium and high exposure compared with patients with low exposure and quantify the resulting health care resource use and costs. RESULTS: The study included 3628 patients (mean age, 57.6 years; 68% female). Patients with medium and high SCS exposure had significantly higher risks of SCS-related complications, including infections and cardiovascular, metabolic, psychiatric, ocular, gastrointestinal, and bone-related complications (odds ratio, 1.23-2.12 by complication; P < .05 for all but one) versus those with low (reference group) SCS exposure. Medium and high SCS exposure were also associated with significantly more emergency department visits (incidence rate ratios, 1.31 [P = .0004] and 1.78 [P < .0001]) and inpatient visits (incidence rate ratios, 1.25 [P < .0001] and 1.59 [P < .0001]) versus low SCS exposure. CONCLUSIONS: A significant dose-response relationship was demonstrated between chronic SCS use and risk of SCS-related complications in patients with severe asthma. Effective SCS-sparing strategies might reduce the burden associated with SCS-related complications in patients with severe asthma.

Clinical and economic burden of COPD in a medicaid population.

OBJECTIVE: To evaluate the clinical and economic burden of COPD patients to Medicaid. STUDY DESIGN: Retrospective, observational matched cohort design. METHODS: We calculated the incremental costs incurred and medical resources used by COPD patients relative to those without COPD. Data were obtained from 8 Medicaid states during 2003-2007. COPD patients were defined as Medicaid beneficiaries ≥40 years with a COPD diagnosis (ICD-9 CM: 491.xx, 492.xx, 496.xx) and treated with maintenance drugs for COPD. Patients were matched (1:3) to Medicaid beneficiaries without a COPD diagnosis on age, gender, race, index year, Medicare/Medicaid dual eligibility, and use of long-term care. Results were stratified by Medicare/Medicaid dual eligibility status and race. RESULTS: A total of 10,221 COPD and 30,663 non-COPD patients were included. Cohorts were on average 65 years of age, 80% White, and 64.8% having Medicare/Medicaid dual eligibility. Inpatient hospitalizations and home healthcare visits/durable medical equipment were primary drivers of incremental medical costs. COPD patients were more than twice as likely to have a hospitalization (odds ratio [95% confidence interval] = 2.32 [2.19, 2.45]) or home healthcare visit/durable medical equipment (2.95 [2.82, 3.08]) compared to non-COPD patients. Medicaid incurred $2118/year in incremental costs due to COPD. On average, incremental costs were 7 times greater for non-dual-eligible patients ($4917) compared to dual-eligible patients ($667), and were more than double for Blacks compared to Whites ($4141 vs $1593). CONCLUSION: COPD imposes a substantial economic and clinical burden on the Medicaid program; this burden differs by dual eligibility status and race.

Healthcare resource use and reimbursement amount by site of care in patients with diffuse large B-cell lymphoma receiving chimeric antigen receptor T-cell (CAR-T) therapy - a retrospective cohort study using CMS 100% Medicare claims database.

Chimeric antigen receptor T-cell (CAR-T) infusion settings may impact healthcare resource use (HRU) and reimbursement amounts. Adults with diffuse large B-cell lymphoma receiving CAR-T therapy were identified from the Centers for Medicare & Medicaid Services (CMS) 100% fee-for-service Medicare database and stratified into inpatient (IP; n = 380) and outpatient (OP; n = 50) cohorts based on CAR-T infusion setting. During the first month post-infusion, OP cohort had significantly fewer IP visits, IP days, intensive care unit (ICU) stays, ICU days, and significantly more OP, emergency room (ER) visits, than IP cohort. In subsequent months, HRU became comparable between cohorts. Medicare reimbursement amounts during the first month post-infusion were nominally higher in the OP vs. IP cohort and comparable in subsequent months. The reimbursement amounts did not reflect the reduced HRU with OP infusions, potentially due to differences in Medicare payment policies for OP vs. IP services.

Observational study on the impact of initiating tiotropium alone versus tiotropium with fluticasone propionate/salmeterol combination therapy on outcomes and costs in chronic obstructive pulmonary disease.

BACKGROUND: This retrospective cohort study compared the risks of exacerbations and COPD-related healthcare costs between patients with chronic obstructive pulmonary disease (COPD) initiating tiotropium (TIO) alone and patients initiating triple therapy with fluticasone-salmeterol combination (FSC) added to TIO. METHODS: Managed-care enrollees who had an index event of ≥ 1 pharmacy claim for TIO during the study period (January 1, 2003-April 30, 2008) and met other eligibility criteria were categorized into one of two cohorts depending on their medication use. Patients in the TIO+FSC cohort had combination therapy with TIO and FSC, defined as having an FSC claim on the same date as the TIO claim. Patients in the TIO cohort had no such FSC use. The risks of COPD exacerbations and healthcare costs were compared between cohorts during 1 year of follow-up. RESULTS: The sample comprised 3333 patients (n = 852 TIO+FSC cohort, n = 2481 TIO cohort). Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation (hazard ratio 0.772; 95% confidence interval [CI] 0.641, 0.930) and any exacerbation (hazard ratio 0.763; 95% CI 0.646, 0.949) and a nonsignificant reduction in COPD-related adjusted monthly medical costs. CONCLUSIONS: Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation and any exacerbation over a follow-up period of up to 1 year. These improvements were gained with triple therapy at roughly equal cost of that of TIO alone.

Observational study of the outcomes and costs of initiating maintenance therapies in patients with moderate exacerbations of COPD.

BACKGROUND: There are limited data describing patients with moderate COPD exacerbations and evaluating comparative effectiveness of maintenance treatments in this patient population. The study examined COPD patients with moderate COPD exacerbations. COPD-related outcomes were compared between patients initiating fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs) following a moderate COPD exacerbation. METHODS: This retrospective observational study used a large administrative claims database (study period: 2003-2009) to identify and describe patients with an initial, moderate COPD exacerbation. A descriptive analysis of patients with moderate COPD exacerbations was done evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and COPD-related costs during a 1-year period. A cohort analysis compared COPD exacerbation rates and associated costs during a variable-length follow-up period between patients initiating maintenance therapy with FSC or ACs. COPD exacerbations were reported as rate per 100 patient-years, and monthly costs were reported (standardized to USD 2009). COPD exacerbation rates between cohorts were evaluated using Cox proportional hazards models, and costs were analyzed using generalized linear models with log-link and gamma distribution. RESULTS: 21,524 patients with a moderate COPD exacerbation were identified. Only 25% initiated maintenance therapy, and 13% had a subsequent exacerbation. Annual costs averaged $594 per patient. A total of 2,849 treated patients (FSC = 925; AC = 1,924) were eligible for the cohort analysis. The FSC cohort had a significantly lower rate of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04). After adjusting for differences in baseline covariates, the FSC cohort had a 42% significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91). The FSC cohort incurred significantly higher adjusted pharmacy costs per patient per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC cohort. However, this increase was offset by a significant reduction in adjusted monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P < 0.05). Total monthly COPD-related costs, as a result, did not differ between cohorts. CONCLUSIONS: Only a quarter of patients with a moderate COPD exacerbation were subsequently treated with maintenance therapy. Initiation of FSC among those treated was associated with better clinical and economic outcomes compared to AC.

Evaluating patient-reported outcome measurement comparability between paper and alternate versions, using the lung function questionnaire as an example.

OBJECTIVES: The goal of this study was to provide recommended steps to assess measurement comparability using a crossover study design and to demonstrate these steps using a short patient-reported outcome (PRO) instrument as an example. METHODS: The example PRO instrument was administered via paper, Web, interactive voice response system, and interview; a randomized crossover design was used to gather data across the multiple administration types. Participants completed the PRO instrument, demographic and health questions, and a short preference questionnaire. Evaluation included comparisons of the item-level responses and agreement, comparison of mean scale scores, score classifications, and questions designed to collect usability and administration preference. Here the authors provide a four-step evaluation guide to evaluate measurement comparability and illustrate these steps using a case-finding tool. RESULTS: In the example, item-level kappa statistics between the paper and the alternate versions ranged from good to excellent, intraclass correlation coefficient for mean scores were above 0.70, and the rate of disagreement ranged from 2% to 14%. In addition, although participants had an administration preference, they reported few difficulties with the versions they were assigned. CONCLUSIONS: The steps described in this article provide a guide for evaluating whether to combine scores across administration versions to simplify analyses and interpretation under a crossover design. The guide recommends the investigation of item-level responses, summary scores, and participant usability/preference when comparing versions, with each step providing unique information to support comprehensive evaluation and informed decisions regarding whether to combine data.

Clinical and economic burden of depression/anxiety in chronic obstructive pulmonary disease patients within a managed care population.

BACKGROUND: Anxiety and depression are common co-morbidities that can complicate the course of chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate their impact on healthcare utilization and costs in a managed care COPD population. METHODS: Administrative claims data were used to conduct a retrospective cohort study of COPD patients ≥ 40 years of age, including those with co-morbid COPD-Depression (including anxiety). COPD-Depression patients were matched to COPD patients without depression (COPD-Only cohort) using propensity scores. Conditional logistic regression models assessed the 1-year risk of COPD exacerbations (i.e., emergency room [ER] visit/inpatient hospitalization) between cohorts. Differences in annual all-cause and COPD-related utilization/costs, along with 2-year costs, were also compared between the cohorts. RESULTS: There were 3,761 patients per cohort. Patients in the COPD-Depression cohort were 77% more likely to have a COPD-related hospitalization (odds ratio [OR] = 1.77, P < 0.001), 48% more likely to have an ER visit (OR = 1.48, P < 0.001), and 60% more likely to have hospitalization/ER visit (OR = 1.60, P < 0.001) compared to the COPD-Only cohort. Average annual all-cause medical cost per patient was $23,759 for COPD-Depression vs $17,765 for COPD-Only (P < 0.001) and total (medical plus pharmacy) cost was $28,961 vs $22,512 (P < 0.001), respectively; corresponding average annual COPD-related medical cost was $2,040 vs $1,392 (P < 0.001) and total cost was $3,185 vs $2,680 (P < 0.001). Similar trends were observed over the 2-year period. CONCLUSIONS: In the COPD population, patients with depression/anxiety have significantly higher risk of COPD exacerbations and annual all-cause and COPD-related costs than patients without these co-morbidities. These findings may have therapeutic implications and seem worthy of further exploration.

Outcomes and costs associated with initial maintenance therapy with fluticasone propionate-salmeterol xinafoate 250 microg/50 microg combination versus tiotropium in commercially insured patients with COPD.

PURPOSE: To compare, in commercially-insured individuals 240 years old, the risk of chronic obstructive pulmonary disease (COPD) exacerbations and COPD-related health care utilization and costs in patients initiating maintenance treatment with fluticasone propionate/salmeterol xinafoate 250 microg/50 microg (FSC) with those in patients initiating treatment with tiotropium bromide (TIO). DESIGN: Retrospective observational cohort study. METHODOLOGY: The risk of COPD exacerbation (moderate, severe, and any), COPD-related health care utilization, and COPD-related costs (overall and by service setting) were assessed over 12 months after the initiation of treatment with FSC or TIO in commercially-insured patients > or =40 years old diagnosed with COPD. PRINCIPAL FINDINGS: After adjusting for covariates, treatment with FSC compared with treatment with TIO was associated with a 14% reduction in risk of severe exacerbation (p = 0.0406), defined as the occurrence of a COPD-related hospitalization; with less health care utilization across several categories of care; with 25% lower COPD-related medical costs ($1814 versus $2258 per patient, p < 0.0001); and with 10% lower COPD-related total costs ($2991 versus $3304 per patient, p < 0.0001) over a 12-month follow-up period. Pharmacy costs were equivalent between FSC and TIO. CONCLUSION: Initiation of maintenance therapy with FSC compared with TIO was associated with significant reductions in the risk of severe exacerbations, health care utilization, and COPD-related medical and total costs. Considered in the context of other findings, these data suggest that earlier maintenance treatment with FSC offers clinical and economic benefits over maintenance treatment with TIO.

The role of combination inhaled corticosteroid/long-acting beta-agonist therapy in COPD management.

Chronic obstructive pulmonary disease (COPD) is now the fourth leading cause of death, affects an estimated 24 million Americans, and accounts for over ten million physician and emergency department (ED) visits and hospitalisations each year. The diagnosis and management of COPD falls largely to primary care practitioners. Previously, COPD management options were limited, but newer treatments have been shown to slow lung deterioration, reduce symptoms and preserve quality of life. Combination therapy with an inhaled corticosteroid and a long-acting beta2-agonist (ICS/LABA) is an effective therapy for COPD that, compared to other therapies, has been shown to reduce exacerbations, hospitalisations, ED visits and health care costs. This review focuses on the role of combination ICS/LABA therapy in managing COPD, including indications, potential benefits and considerations that affect therapy decisions.

Quantification of Economic Impact of Drug Wastage in Oral Oncology Medications: Comparison of 3 Methods Using Palbociclib and Ribociclib in Advanced or Metastatic Breast Cancer.

BACKGROUND: Discarding unused drugs after dose changes or discontinuation can significantly affect pharmacy budgets. This is especially concerning for expensive oncology agents. However, few economic studies account for drug wastage, providing an inaccurate estimate of a drug's actual economic cost, cost-effectiveness, and value. OBJECTIVES: To (a) compare the economic impact of drug wastage between ribociclib and palbociclib-clinically similar oral medications for metastatic breast cancer-using 3 approaches (Markov model, pharmacy acquisition cost model, and a retrospective claims analysis) and (b) compare the modeling results with a published estimate of drug wastage for palbociclib from a claims analysis. METHODS: A Markov model and a pharmacy acquisitions cost model were developed to evaluate the economic impact of dose reductions for ribociclib and palbociclib over a 1-year time period. Data inputs were pharmacy costs (RED BOOK wholesale acquisition cost) and proportion of patients experiencing dose reductions from either ribociclib randomized clinical trials (MONALEESA-2, -3, or -7) or real-world observational data (Symphony Health retrospective claims analysis). The latter constituted the third approach for quantifying drug wastage. The economic impact of dose reductions for ribociclib and palbociclib in postmenopausal women with previously untreated HR-positive/HER2-negative advanced breast cancer was assessed. Drug wastage was defined as drug doses that could not be used by a patient following a dose reduction. The cost of drug wastage was defined as the cost associated with an unused drug resulting from a dose reduction. The predicted results from the 2 models were compared with a previously published claims analysis that estimated the effect of treatment costs and drug wastage for palbociclib based on the observed dosing patterns from the Symphony Health Solutions database. RESULTS: In the Markov model, relative to ribociclib, palbociclib users experienced drug wastage of $112,382 total, or $1,124 per treated patient, per year due to dose changes. In the pharmacy acquisition cost model, relative to ribociclib, palbociclib usage was associated with an increased cost of $7,196 per patient per year (based on a mid-cycle dose reduction) comprising dosing-based cost differences and drug wastage cost for palbociclib of $3,727. The previously published claims analysis found that palbociclib users experiencing a dose reduction had drug wastage costs of $5,471 per patient. CONCLUSIONS: In both models, dose reductions for ribociclib patients resulted in no wastage, since unused tablets could be administered in subsequent cycles, while dose reductions for palbociclib resulted in drug wastage and increased costs. The results from both models were consistent with previously published results from the claims analysis, demonstrating drug wastage costs for palbociclib. DISCLOSURES: This study received financial support from Novartis Pharmaceuticals, which has products approved for treatment of breast cancer. Tang was employed by Novartis during this study; Zacker and Dalal are employed by Novartis and own company stock. Biskupiak, Brixner, and Oderda received payment from Novartis for this study. Brixner serves as a consultant for Millcreek Outcomes Group and also declares consulting fees from Abbvie, AstraZeneca, Abbott, Becton Dickinson, and Xcenda, unrelated to this study.

Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study.

BACKGROUND: In the Mammary Oncology Assessment of LEE011's (Ribociclib's) Efficacy and Safety (MONALEESA-2) study, combination treatment with the selective inhibitor of cyclin-dependent kinases 4/6 ribociclib with letrozole significantly improved progression-free survival (PFS) versus letrozole alone in postmenopausal women with hormone receptor-positive HR+/HER2- advanced breast cancer (ABC). Herein we present results from the subset of US patients enrolled in MONALEESA-2. PATIENTS AND METHODS: Postmenopausal women with HR+/HER2- ABC without previous treatment for advanced disease were randomized (1:1) to ribociclib 600 mg/d (3 weeks on/1 week off) with letrozole 2.5 mg/d (continuous) or placebo with letrozole. The primary end point was locally assessed PFS. RESULTS: Overall, 213 US patients were enrolled in MONALEESA-2 (ribociclib, n = 100; placebo, n = 113). Baseline characteristics were similar between treatment groups and consistent with the global population. With a median follow-up of 27 months, 38 (38%) and 29 (26%) patients in the ribociclib and placebo groups, respectively, had continued to receive treatment. Median PFS was 27.6 months with ribociclib and 15.0 months with placebo (hazard ratio, 0.53). The most common all-cause adverse events were neutropenia (ribociclib, 72.0% [n = 72]; placebo, 4.6% [n = 5]), nausea (ribociclib, 69.0% [n = 69]; placebo, 44.0% [n = 48]), and fatigue (ribociclib, 60.0% [n = 60]; placebo, 50.5% [n = 55]). Two patients (ribociclib, 2.0%; placebo, 0%) experienced febrile neutropenia. CONCLUSION: In the US subset of MONALEESA-2, ribociclib with letrozole showed superior efficacy versus letrozole alone. These findings are consistent with the global population and support first-line use of ribociclib with letrozole in patients with HR+/HER2- ABC.

COPD affects worker productivity and health care costs.

Purpose: This study aimed to measure the true burden of COPD by calculating incremental direct and indirect costs. Direct medical resource use, productivity metrics, and COPD-specific resource use and costs were also evaluated. Patients and methods: This was a retrospective, observational, matched cohort study using administrative claims data from the Truven Health MarketScan® Commercial Claims and Encounters and the Health and Productivity Management databases (2007-2010). Working-age (18-65 years) patients with COPD were identified as having at least one hospitalization or one emergency department visit or two outpatient visits. Patients in the non-COPD cohort did not have a diagnosis of COPD during the study period. Outcomes were evaluated in the first full calendar year after the year of identification (index). Results: Of the 5,701 patients with COPD identified, 3.6% patients were frequent exacerbators (≥2), 10.4% patients were infrequent exacerbators (1), and 86% patients were non-exacerbators (0). When compared with the 17,103 patients without COPD, the incremental direct cost of COPD was estimated at $6,246/patient/year (95% confidence interval: $4,620, $8,623; P<0.001). Loss in productivity was significantly greater in patients with COPD, with an average of 5 more days/year of absence from work and incremental indirect costs from short-term disability of $641 (P<0.001). Direct costs for frequent exacerbators ($17,651/year) and infrequent exacerbators ($14,501/year) were significantly higher than those for non-exacerbators ($11,395, P<0.001). Conclusion: Working-age patients with COPD incur statistically significantly higher direct and indirect costs and use more resources compared with those who do not have COPD.

Treatment patterns, clinical and economic outcomes of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer receiving ceritinib: a retrospective observational claims analysis.

Objective: To describe patient characteristics, treatment patterns, healthcare resource utilization (HRU), and costs among patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) receiving ceritinib in second or later line of therapy. Methods: Adult patients with NSCLC receiving ceritinib were identified from two large US claims databases (2006-2015). Patient characteristics, comorbidity profile, treatment patterns prior to ceritinib, and ceritinib dosing patterns were described. All-cause, HRU, and costs incurred during the observation period after ceritinib initiation were reported per patient per six months. Results: One hundred sixty-four patients were included (mean age 54.2 years, 57.3% female); the majority had metastatic disease (94.5%) and the average Charlson Comorbidity Index was 7.6. 150 (91.5%) patients received crizotinib prior to ceritinib - average crizotinib duration was 10.2 months and time between crizotinib discontinuation and ceritinib initiation was 2.1 months (median= 0; 25th-75th percentile= 0-0.8). Most patients (73.8%) initiated ceritinib on the recommended dose (750 mg) and maintained the dose until the end of the observation period (mean of 7.4 months) or ceritinib discontinuation; 61 (37.2%) patients discontinued ceritinib during the observation period. A total of 76 (46.3%) patients had at least one inpatient admission during the observation period after ceritinib initiation. Mean total healthcare cost per patient per six months was $111,468. Conclusions: Patients with ALK-positive NSCLC receiving ceritinib had a high comorbidity burden and generally started ceritinib on the recommended dose quickly after crizotinib discontinuation. Medical costs accounted for nearly a half of the total healthcare costs.

Economic analysis of BRAF gene mutation testing in real world practice using claims data: costs of single gene versus panel tests in patients with lung cancer.

AIMS: To assess the time to BRAF testing, compare the characteristics of tested vs not-tested patients, and describe the costs for sequential vs next-generation sequencing (NGS) BRAF testing. METHODS: Patients diagnosed with lung cancer after December 1, 2013 were identified from two US claims databases; their characteristics were assessed during the 12 months before diagnosis (index date). Testing modalities were analyzed from the index date to end of continuous health plan enrollment or data availability (December 2015), based on combinations of Current Procedural Terminology (CPT) procedure codes. Time to BRAF testing was assessed using Kaplan-Meier analysis. Costs were analyzed from a payer's perspective. RESULTS: A total of 28,011 patients newly-diagnosed with lung cancer were identified. Of them, 1,260 (4.5%) were tested for BRAF: 3.2% and 4.2% were tested at 6 and 12 months, respectively, after the index date. Compared to non-tested patients, tested patients were younger (58.3 vs 65.3 years; p < .001), had a lower Charlson Comorbidity Index (2.8 vs 2.9; p = .005), and a higher proportion had metastases (70.9% vs 43.4%; p < .001). In 76.0% of cases, BRAF was tested along with KRAS. BRAF was tested using NGS in 6.6% of cases. The average reimbursed amounts for the 10 most common CPT code combinations were $207-$2,074. Using the average costs of individual mutation tests, the total cost of sequential testing comprising KRAS, EGFR, ALK, ROS1, and BRAF tests was $3,763 ($464, $696, $1,070, $1,127, and $406, respectively), that of NGS was $2,860. LIMITATIONS: Claims data did not include BRAF test results. CONCLUSIONS: Among patients newly-diagnosed with lung cancer, 4.5% were tested for BRAF. Tested patients were younger and had a lower comorbidity burden, but more advanced disease. While reimbursed amounts varied greatly based on combinations of testing procedures, NGS testing was associated with cost savings compared to sequential testing of individual mutations.

Treatment and Monitoring Patterns Among Premenopausal Women with HR+/HER2- Advanced Breast Cancer.

INTRODUCTION: Premenopausal women with hormone receptor positive (HR+) and human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (aBC) often present with aggressive tumor types that lead to poor prognosis, high rates of recurrence, and mortality. Although clinical guidelines provide evidence-based recommendations for optimal treatment and monitoring, there is a dearth of information regarding treatment and monitoring patterns in clinical practice. In this study, we describe treatment and monitoring patterns among premenopausal women with HR+/HER2- aBC in real-world practice. METHODS: A large US claims database was used to describe treatment patterns for patients in first, second, and third lines of therapy. Treatment monitoring included complete blood count (CBC), liver function test (LFT), and electrocardiogram (EKG) monitoring, described for the first three lines of therapy, and separately for patients receiving endocrine monotherapy (ET) and chemotherapy. RESULTS: Among 3203 patients, chemotherapy was the most common treatment used in first-line (63.6%) and second-line therapy (66.9%). ET was used in 34.4, 30.1, and 73.6% of patients in first, second, and third lines of therapy, respectively. The two most common treatment sequences were a single line of ET (27.3%), and two consecutive lines of chemotherapy followed by a line of ET (19.3%). Patients receiving chemotherapy were monitored with CBC on average more than two times per month, and for LFT one to two times per month. Patients receiving ET were monitored with CBC and LFT on average once every 2-3 months. Overall, approximately 20% of patients were monitored with an EKG at some point during each line of therapy. CONCLUSION: A considerable proportion of premenopausal women with aBC received first- and second-line chemotherapy, which appears inconsistent with current clinical guidelines. The observed treatment heterogeneity points to a lack real-world consensus on the management of premenopausal women with HR+/HER2- aBC. FUNDING: Novartis Pharmaceuticals Corporation.

Dosing Patterns and Economic Burden of Palbociclib Drug Wastage in HR+/HER2- Metastatic Breast Cancer.

INTRODUCTION: Targeted therapies have revolutionized the treatment of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC). However, as for many oncology drugs, the dose of targeted therapies may need to be adjusted over time, leading to drug wastage when a dose modification is needed but the dose cannot be split or saved. This has been shown to be the case for palbociclib and has led to concerns among payers. This study described palbociclib dosing patterns and estimated the economic burden of the drug wastage associated with palbociclib dose modifications in postmenopausal women with HR+/HER2- mBC. METHODS: A large US claims database was used to identify postmenopausal women with HR+/HER2- mBC who received a palbociclib-based therapy during one of their first three lines of therapy for mBC between February 2015 (palbociclib approval) and December 2015. Dosing patterns (dosing modifications and sequences) were reported; a dose modification was defined as an increase/decrease of at least 25 mg daily compared to the preceding dose. Estimates of drug wastage costs were based on days with overlap in prescription fills for different palbociclib doses. RESULTS: A total of 473 postmenopausal palbociclib-treated women with HR+/HER2- mBC were included (first line 214; second line 157; third line 120). Over an average duration of line of therapy of approximately 4 months, dose modification was observed in 17.8%, 31.2%, and 35.0% of patients in first, second, and third line. Average overlap in prescription fills was 9.2, 9.9, and 5.4 days in first, second, and third line. This potential drug wastage resulted in an average cost of $4376, $4740, and $2592 per patient in first, second, and third line. CONCLUSIONS: This study showed that drug wastage due to palbociclib dose modification results in substantial costs. Treatment options with more flexible dosing may help reduce the costs of drug wastage. FUNDING: Novartis Pharmaceuticals Corporation.

Progression-free survival with endocrine-based therapies following progression on non-steroidal aromatase inhibitor among postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative metastatic breast cancer: a network meta-analysis.

OBJECTIVE: To quantify the comparative efficacy of currently available endocrine-based therapies (ETs) for postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (mBC) after non-steroidal aromatase inhibitor (NSAI) progression. DESIGN: Network meta-analysis (NMA). METHODS: Randomized clinical trials of ETs for HR+/HER2- mBC were identified via a systematic literature review using MEDLINE, Embase, Cochrane Library and key conference proceedings. All trials met the following inclusion criteria: (1) included women with HR+/HER2- mBC; (2) previous treatment with ETs or chemotherapy as first-line therapy; (3) treatment with ET as monotherapy or in combination with targeted therapy; (4) progression-free survival (PFS) was reported; and (5) published in 2007 (when HER2 testing became standardized) or later. Regimens were compared using pairwise hazard ratios (HRs) and 95% credible intervals (CrIs) of PFS obtained from a Bayesian NMA. Treatments with different approved dosages were pooled into the same arm; anastrozole and exemestane were pooled as aromatase inhibitors (AIs) due to clinical similarities. RESULTS: A total of 4 trials and 6 regimens (palbociclib + fulvestrant, everolimus + fulvestrant, everolimus + AI, fulvestrant + AI, fulvestrant and AI) were eligible for inclusion. Palbociclib + fulvestrant and everolimus + AI had 50% and 55% reduced hazard of progression or death vs. AI (95% CrI upper bound ≤1), respectively. Palbociclib + fulvestrant, everolimus + AI and everolimus + fulvestrant had 54%, 58% and 40% reduced hazard vs. fulvestrant (95% CrI upper bound ≤1), while palbociclib + fulvestrant and everolimus + AI had 52% and 55% reduced hazard vs. fulvestrant + AI (95% CrI upper bound ≤1), respectively. CONCLUSION: Postmenopausal women with HR+/HER2- mBC who had previously failed an NSAI and received palbociclib + fulvestrant, everolimus + AI or everolimus + fulvestrant had longer PFS compared to those who received fulvestrant or AI alone.

Economic Burden of HR+/HER2- Metastatic Breast Cancer Among Adult Premenopausal Women.

INTRODUCTION: Premenopausal women with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) have complex treatment needs and may receive sequential combinations of endocrine therapy (ET) or chemotherapy. This study describes healthcare utilization (HRU) and costs among premenopausal women with HR+/HER2- mBC in real-world settings from a payer's perspective. METHODS: In this retrospective cohort study, premenopausal women with HR+/HER2- mBC who received ET or chemotherapy were identified from the Truven Health Analytics MarketScan database (1 January 2006-31 December 2015). The main HRU outcomes per patient per 6 months (PPP6 M) were measured during each line of therapy and included number of days in inpatient (IP) and outpatient (OP) services. Healthcare costs per patient per month (PPPM) included medical and pharmacy costs. RESULTS: A total of 3203 patients received first-line, 2194 received second-line, and 1242 received third-line therapy for mBC. Mean number of IP days PPP6 M were 1.6, 1.3, and 1.5 days in the first, second, and third lines, respectively. Mean number of days with OP services PPP6 M was 31.4, 30.9, and 23.3 in the first, second, and third lines, respectively. Among patients receiving ET, mean total healthcare costs were $6521, $4440, and $4555 PPPM in the first, second, and third line, respectively. Among patients receiving chemotherapy, mean total healthcare costs were $16,842, $12,868, and $16,129 PPPM in the first, second, and third line, respectively. These costs were mainly driven by treatment and OP costs. CONCLUSION: Real-world HRU and costs among premenopausal women with HR+/HER2- mBC are extensive. Patients who received chemotherapy incurred approximately twice the costs of patients treated with ET. FUNDING: Novartis Pharmaceutical Corp.