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.

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.

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 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.

Budget impact of including ribociclib in combination with letrozole on US payer formulary: first-line treatment of post-menopausal women with HR+/HER2- advanced or metastatic breast cancer.

OBJECTIVES: The combination of a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor with the aromatase inhibitor letrozole is a safe and effective alternative to letrozole monotherapy for first-line hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This study evaluates the budget impact of using the CDK 4/6 inhibitor ribociclib plus letrozole as a first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer, from a United States (US) payer perspective. METHODS: A cohort-based budget impact model was used to calculate the incremental cost of introducing ribociclib plus letrozole over three years for the target population. The analysis compared two scenarios: treatment options excluding or including ribociclib plus letrozole. Market shares were derived from market research and the assumption was the introduction of ribociclib plus letrozole would only displace existing CDK-based therapies. Treatment duration was based on the median time to treatment discontinuation or median progression-free survival for first-line treatment, and on clinical trial data for second- and third-line treatment. Acquisition costs were based on wholesale acquisition costs and considered co-payment. Costs for drug administration and monitoring, subsequent therapy, and relevant adverse events were included. RESULTS: Of 1 million insured members, 263 were eligible for CDK 4/6 inhibitor treatment. Cumulative total savings with ribociclib plus letrozole were $3.01M over three years, corresponding to a cumulative incremental cost saving of $318.11 per member treated per month. CONCLUSIONS: In the US, ribociclib plus letrozole represents a cost-saving first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer.

Monitoring of Hematologic, Cardiac, and Hepatic Function in Post-Menopausal Women with HR+/HER2- Metastatic Breast Cancer.

INTRODUCTION: In the treatment of metastatic breast cancer (mBC), regular monitoring is key in helping physicians to make informed clinical decisions, managing treatment side effects, and maintaining patients' quality of life. Therefore, we investigated the monitoring frequency in post-menopausal women with HR+/HER2- mBC stratified by first-line regimen. METHODS: Treatment monitoring was assessed using two complementary data sources: a medical chart review (chart review analysis) and a commercial claims database (claims analysis). Women with post-menopausal HR+/HER2- mBC who initiated first-line therapy for mBC were selected and classified under three cohorts, based on treatment received: cyclin-dependent kinase 4/6 (CDK4/6) inhibitor (i.e., palbociclib-the only CDK4/6 approved at the time of the study), endocrine therapy (ET), and chemotherapy. Frequency of monitoring [complete blood count (CBC), electrocardiogram (EKG), and liver function test (LFT)] and laboratory abnormalities detected during the first line of therapy were analyzed. RESULTS: In the chart review analysis, 64 US oncologists abstracted medical information on 401 eligible patients, including 210 CDK4/6 users, 121 ET users, 51 chemotherapy users; 19 patients used other regimens. All patients had ≥ 1 CBC; between 8.3% (ET users) and 39.5% (CDK4/6 users) had ≥ 1 EKG; and over 98% of patients had ≥ 1 LFT across all three cohorts. Among monitored patients, 64.6% had a CBC abnormality, with anemia (39.9%), leukopenia (27.4%), and neutropenia (26.7%) being the most common. Abnormal EKG readings were detected in 8.4, 0.0%, and 7.7% of CDK4/6, ET, and chemotherapy users, respectively. LFT abnormalities were detected in 14.1-26.0% of CDK4/6 and chemotherapy users, respectively. Similar frequency of monitoring was observed in the claims analysis, with the exception of EKG monitoring, for which the proportion of patients tested was higher. CONCLUSION: Post-menopausal women with HR+/HER2- mBC receiving first-line therapy with CDK4/6, ET, or chemotherapy were regularly monitored regardless of the first-line regimen received. 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.

Cost-Effectiveness of Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective.

BACKGROUND: U.S. regulatory approvals of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors ribociclib and palbociclib as add-ons to letrozole greatly enhance the prospects for treating postmenopausal women with hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer. Clinical trials have established that the combination of a CDK 4/6 inhibitor with letrozole can significantly improve progression-free survival (PFS) versus letrozole monotherapy and is safe and well tolerated. Cost-effectiveness studies are required to inform payers and clinical decision makers on the money value of combination treatment in clinical practice. OBJECTIVE: To evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole and versus letrozole monotherapy in the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer from a U.S. private third-party payer perspective. METHODS: A partitioned survival model including 3 health states (progression free, with either overall response or stable disease; progressed disease; and death) simulated lifetime costs and outcomes over a 40-year lifetime horizon with a 1-month cycle length. Clinical efficacy data (PFS and overall survival [OS]) were derived from a phase III trial of ribociclib plus letrozole (MONALEESA-2; NCT01958021), a phase II trial of palbociclib plus letrozole (PALOMA-1; NCT00721409), and a Bayesian network meta-analysis. Health care costs included drug acquisition and monitoring, disease management, subsequent therapies, and serious drug-related adverse events. Effectiveness was measured in life-years, derived from survival projections, and in quality-adjusted life-years (QALYs), calculated from time spent in each state combined with health-state utility values. A one-way deterministic sensitivity analysis explored the impact of uncertainty in key model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis. RESULTS: Ribociclib plus letrozole was dominant versus palbociclib plus letrozole, with a cost saving of $43,037 and a gain of 0.086 QALYs. Compared with letrozole monotherapy, ribociclib plus letrozole was associated with an incremental cost of $144,915 and an incremental QALY of 0.689, equating to an incremental cost-effectiveness ratio of $210,369 per QALY. Key model drivers included OS HRs for palbociclib plus letrozole versus letrozole and for ribociclib plus letrozole versus letrozole, the PFS HR for palbociclib plus letrozole versus letrozole, PD health-state costs, utility of response, and cost discount rate. The probabilities that ribociclib plus letrozole was cost-effective versus letrozole at thresholds of $50,000, $100,000 and $200,000 per QALY gained were 1.6%, 6.3%, and 50.5%, respectively. CONCLUSIONS: In the United States, ribociclib plus letrozole is a cost-effective alternative to palbociclib plus letrozole for the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer. Ribociclib plus letrozole is also cost-effective versus letrozole monotherapy at willingness-to-pay thresholds greater than $198,000 per QALY (for probabilistic analysis). DISCLOSURES: Funding for this study was provided by Novartis, which manufactures ribociclib and provided input on the study design and data collection, analysis, and interpretation. Mistry, May, Suri, and Young are employees of PAREXEL. Tang, Mishra, D. Bhattacharyya, and Dalal are employees of Novartis. S. Bhattacharyya was an employee of Novartis during the study period. Tang and Dalal hold stock in Novartis. Brixner, Oderda, and Biskupiak were paid by Millcreek Outcomes Group as consultants for work on this project. Brixner has also consulted for AstraZeneca, UCB, Regeneron, and Abbott.

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.

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.

Progression-free Survival With First-line Endocrine-based Therapies Among Postmenopausal Women With HR+/HER2- Metastatic Breast Cancer:: A Network Meta-analysis.

PURPOSE: The comparative efficacy of endocrine-based therapies (ETs) for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) is not well characterized. This network meta-analysis (NMA) synthesized available evidence on progression-free survival (PFS) with first-line ETs for postmenopausal HR+/HER2- mBC. METHODS: A systematic literature review identified randomized controlled trials of first-line ETs. Pairwise hazard ratios and 95% credible intervals (CrIs) were obtained via a Bayesian NMA model. Subgroup NMAs were conducted among late progressors (disease-free interval ≥12 months from completion of [neo] adjuvant therapy with letrozole or anastrozole at the time of randomization) and de novo patients, defined as patients whose initial BC diagnosis is mBC. FINDINGS: Five trials and 5 regimens (ribociclib + an aromatase inhibitor [AI] [LEE + AI], palbociclib + AI [Pal + AI], fulvestrant 250 mg + AI [Ful250 + AI], fulvestrant 500 mg [Ful500], and AI) were selected. LEE + AI, Pal + AI, Ful250 + AI, and Ful500 had significantly longer PFS versus AI (95% CrI upper-bound ≤1). LEE + AI had a 30% and 29%, and Pal + AI had a 31% and 30%, reduced hazard of progression or death versus Ful250 + AI and Ful500 (95% CrI upper-bound ≤1), respectively. The probability of being the most efficacious was 46% for LEE + AI and 54% for Pal + AI. In subgroup analyses among late progressors, LEE + AI had a 4% reduced hazard of progression or death versus Pal + AI but was not statistically significant. In the de novo analysis, Pal + AI and LEE + AI had a 29% and 40% reduced hazard of progression or death versus Ful500, respectively, but were not statistically significant. In both subgroup analyses, all therapies had significantly longer PFS compared with AI. IMPLICATIONS: Pal + AI, LEE + AI, Ful250 + AI, or Ful500 as first-line treatment for HR+/HER2- mBC had longer PFS than AI alone. Given the lack of head-to-head clinical trials comparing the efficacy of recently approved first-line ETs for HR+/HER2- mBC, these results have important clinical implications for the treatment of 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.

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.

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.

Current Treatment Patterns Among Postmenopausal Women with HR+/HER2- Metastatic Breast Cancer in US Community Oncology Practices: An Observational Study.

INTRODUCTION: Recent approval of novel agents has changed the treatment landscape for post menopausal women with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer (mBC). The objective of this study was to describe contemporary treatment patterns among postmenopausal women with HR+/HER2- mBC in the real-world setting. METHODS: Data were collected from 64 community oncologists in the US between February and June 2017 using an online medical records extraction tool. Physicians reviewed medical records and provided information on patient demographics and disease characteristics, and treatment regimens. Treatment patterns were described overall and separately by line of therapy and type of treatment received. Discontinuation rates were estimated using Kaplan-Meier analyses to account for censoring. RESULTS: Data were collected on 401 patients. Mean age at the time of mBC diagnosis was 67 years. In the first-line setting, 52.4% of patients received a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based regimen, most commonly with an aromatase inhibitor (AI) (39.2%) or fulvestrant (10.0%); 30.2% received endocrine therapy, most commonly an AI (21.4%) or fulvestrant (5.2%) in monotherapy, while 12.7% received a chemotherapy-based regimen. In the second-line setting, 42.9% of patients received a CDK4/6 inhibitor-based regimen, 18.4% received endocrine therapy, and 22.4% received a chemotherapy-based regimen. The 18-month discontinuation rate was 34.5% for patients receiving a CDK4/6 inhibitor-based regimen and 45.8% for patients receiving endocrine monotherapy. CONCLUSION: CDK4/6 inhibitor-based regimens were the most commonly prescribed treatment in both first- and second-line settings. A wide variety of treatment sequences were observed which suggests an absence of a standard of care for postmenopausal women with HR+/HER2- mBC in real-world practice.

Clinical and economic burden of dyspnea and other COPD symptoms in a managed care setting.

PURPOSE: The degree to which symptoms such as dyspnea affect patients with COPD is individualized. To address the gap between clinical symptom measures and self-perceived disease burden, we investigated the symptom status of adult patients with COPD and followed with an administrative claims analysis of health care resource utilization and costs. METHODS: This was a hybrid US observational study consisting of a cross-sectional patient survey followed by a retrospective analysis of administrative claims data. The primary COPD symptom measures were the modified Medical Research Council (mMRC) Dyspnea scale and the COPD Assessment Test (CAT). RESULTS: A total of 673 patients completed the survey. Of these, 65% reported mMRC grades 0-1 (low symptomatology) and 35% reported mMRC grades 2-4 (high symptomatology); 25% reported CAT score <10 (low symptomatology) and 75% reported CAT score ≥10 (high symptomatology). More patients with high symptomatology (by either measure) had at least one COPD-related inpatient hospitalization, emergency room visit, physician office visit, or other outpatient services, and filled at least one COPD-related prescription medication vs patients with low symptomatology. COPD-related costs were higher for patients with high symptomatology than patients with low symptomatology. In a multivariate analysis, COPD-related costs were also higher in patients reporting severe symptoms. CONCLUSION: Patients with high COPD symptomatology utilized more health care resources and had higher COPD-related health care costs during the 6-month post-survey period than patients with low symptomatology.

Monitoring for and Characterizing Crizotinib Progression: A Chart Review of ALK-Positive Non-Small Cell Lung Cancer Patients.

INTRODUCTION: Crizotinib is recommended as first-line therapy for ALK-positive non-small cell lung cancer (NSCLC), but within a year of treatment initiation many patients develop resistance. With the recent approval of second-generation ALK inhibitors, this study assessed how physicians monitor for and diagnose progression and how they alter treatment following progression on crizotinib. METHODS: A panel of oncologists from the United States were surveyed regarding their monitoring practices and criteria for diagnosing progression on crizotinib. The physicians also retrospectively provided data (March-June 2016) from the medical charts of their adult patients with locally advanced or metastatic ALK-positive NSCLC who progressed on crizotinib after the approval (April 2014) of the first second-generation ALK inhibitor, ceritinib. RESULTS: A total of 28 physicians responded to the survey. Data was abstracted on 74 patients. In the physician survey, most physicians (71%) reported monitoring for radiographic progression every 3-4 months. When new lesions were detected, physician response varied. Following a symptomatic isolated lesion, most physicians (75%) would add local therapy and resume crizotinib. Following multiple symptomatic lesions, 96% and 64% of physicians would switch to a new therapy depending on whether the lesions were extracranial or isolated to the brain, respectively. For the patient cohort, physician-defined progression on crizotinib was diagnosed after a median of 10 months, and within 30 days of diagnosis, 86% of patients discontinued crizotinib. Among all patients who discontinued crizotinib, 77% switched to ceritinib, 14% to chemotherapy, and 1% to alectinib. The remaining 7% did not receive additional systemic antineoplastic therapy. CONCLUSION: The findings from this physician survey and retrospective chart review study suggest that physician response to the development of new lesions in crizotinib-treated ALK-positive NSCLC patients varies with location and extent of the lesions. Once patients were considered to have progressed, most of them were immediately switched to ceritinib. FUNDING: Novartis Pharmaceuticals Corporation.

Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer Patients Receiving Ceritinib: A Chart Review Study.

INTRODUCTION: This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. METHODS: US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib. RESULTS: Medical charts of 58 ALK-positive NSCLC patients treated with ceritinib were reviewed (median age 63 years; 41% male; 21% with prior chemotherapy experience). At ceritinib initiation, 44 patients had multiple distant metastases, most commonly in the liver (60%), bone (53%), and brain (38%). Initial ceritinib dose varied: 71% received 750 mg, 19% 600 mg, and 10% 450 mg. Although median follow-up after ceritinib initiation was short (3.8 months), most patients achieved either a complete or partial response (69%) on ceritinib, regardless of metastatic sites present at initiation or initial dose. Median PFS on ceritinib was 12.9 months. 17% of patients had a gastrointestinal AE reported during follow-up. The majority of events occurred in patients instructed to fast; no patients instructed to take a lower dose of ceritinib with food reported gastrointestinal AEs. CONCLUSION: These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs. Future studies with larger sample size and longer follow-up are warranted, including an ongoing randomized trial to assess the gastrointestinal tolerability of ceritinib 450 and 600 mg with low-fat meals. FUNDING: Novartis Pharmaceutical Corporation.