Andrew Kageleiry

Real-world patterns of endocrine therapy for metastatic hormone-receptor-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2−) breast cancer patients in the United States: 2002–2012

Abstract Objective: Clinical guidelines recommend that patients with HR+/HER2− metastatic breast cancer (mBC), the most prevalent mBC subtype, receive three lines of endocrine therapy (ET) prior to transitioning to chemotherapy (CT) in the absence of need for rapid response, symptomatic visceral disease, or suspected endocrine resistance. Little is known about real-world ET treatment patterns among HR+/HER2− mBC patients. Research design and methods: Post-menopausal women with HR+/HER2− mBC were identified in the MarketScan databases (2002Q3–2012Q2). Patients were classified as receiving either ET or CT as their first therapy post-mBC diagnosis. Those receiving ET were studied further and stratified into three subgroups based on which of the following events occurred first: transition to CT, discontinuation of ET (90 days without evidence of ET), or end of data or insurance eligibility. Main outcome measures: Mean numbers of lines of ET and median durations of each line were summarized for the overall sample and subgroups. Results: Among a total of 19,120 HR+/HER2− mBC patients, 11,545 (60%) initiated an ET; median follow-up time for these patients was 17 months. Seventy-four percent did not receive a second ET. The average patient received 1.36 lines of ET. Among patients with 2+ lines of ET, the duration of each subsequent line was significantly shorter than the previous line. Results were similar in all subgroups. Limitations: Clinical characteristics and reasons for treatment choices are unavailable in claims data. Conclusions: Fewer than two thirds of patients initiated treatment for HR+/HER2− mBC with ET. Among those who did, most received only one line of ET before discontinuation or transition to CT. Patients who received multiple lines of ET experienced shorter durations of therapy with each line. Real-world treatment with ET falls short of the targets recommended by guidelines, representing unmet need for treatment options that improve the effectiveness of endocrine therapy.

Characteristics, treatment patterns, and survival among ALK+ non-small cell lung cancer (NSCLC) patients treated with crizotinib: A chart review study

OBJECTIVES Second-generation ALK inhibitors are recently available for ALK+ non-small cell lung cancer (NSCLC) patients previously treated with crizotinib. This study described characteristics, treatment sequencing, and outcomes among locally advanced/metastatic crizotinib-experienced ALK+ NSCLC patients. MATERIALS AND METHODS From July 2014 to June 2015, a retrospective patient chart review was conducted among physicians from the US, EU, Korea, and Latin America. Participating clinicians identified their ALK+ NSCLC patients who received crizotinib and reported on their clinical characteristics, treatments, and survival using a pre-defined case report form. Kaplan-Meier analyses were used to describe overall survival (OS) and clinician-defined progression-free survival (PFS). RESULTS Participating clinicians reviewed charts of 158 ALK+ NSCLC patients treated with crizotinib during the study period. Crizotinib was most commonly received in the second-line setting (41% of patients), though this varied across geographical regions. Roughly half (53%) of the patients who discontinued crizotinib received further antineoplastic therapy; second-generation ALK inhibitors (44%) and chemotherapy (42%) regimens were used most frequently. Following crizotinib discontinuation, median OS was 8.2 months. Among patients who did not initiate a second-generation ALK inhibitor following crizotinib, median OS was 4.9 months; among those who did, median OS was not reached. Among patients who received chemotherapy immediately following crizotinib discontinuation, time to clinician-defined PFS from post-crizotinib chemotherapy initiation was 3.6 months. CONCLUSION Following crizotinib discontinuation, many patients received no further antineoplastic therapy, and OS was poor among patients who did not receive a second-generation ALK inhibitor. Recently available second-generation ALK inhibitors may provide important treatment options for ALK+ NSCLC patients.

Impact of Paliperidone Palmitate Versus Oral Atypical Antipsychotics on Health Care Resource Use and Costs in Veterans with Schizophrenia.

OBJECTIVE To compare health care resource utilization and costs in veterans with schizophrenia treated with paliperidone palmitate (PP) versus oral atypical antipsychotics (OAAs). METHODS A retrospective longitudinal study was conducted using electronic health record data from the Veterans Health Administration. Veterans with schizophrenia (identified using ICD-9-CM 295.x) initiating PP or OAAs between January 2010 and October 2014, with ≥ 12 months of benefits enrollment prior to treatment initiation and ≥ 6 months of enrollment after treatment initiation, and with ≥ 1 Global Assessment of Functioning measurement at baseline were included. Inverse probability of treatment weighted regression models were used to estimate incidence rate ratios (IRRs) and cost differences (CDs) for the impact of PP versus OAAs on health care resource utilization and costs. RESULTS Among 10,290 eligible veterans, 2,285 and 8,005 were initiated on PP and OAAs, respectively. After adjustment, PP was associated with less frequent all-cause inpatient hospitalizations (IRR = 0.89, P < .001) and more frequent mental health intensive case management visits (IRR = 1.81, P < .001) compared to OAAs. PP treatment was associated with higher likelihood of increased income (odds ratio [OR] = 1.20, P = .027) and lower likelihood of homelessness (OR = 0.82, P < .001). While mean annual pharmacy and outpatient costs were higher among PP users (CD =

Clinical Outcomes Associated with Switching or Discontinuation from Anti-TNF Inhibitors for Nonmedical Reasons

3,417 pharmacy,

Time on treatment of everolimus and chemotherapy among postmenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative metastatic breast cancer: a retrospective claims study in the US

2,527 outpatient, P < .001), mean annual inpatient costs were lower (CD = -

The epidemiology and targeted therapies for relapsed and refractory CD30+ lymphomas

14,456, P < .001), resulting in average annual total health care (medical and pharmacy) cost savings associated with PP (CD = -

Cost of adverse events during treatment with everolimus plus exemestane or single-agent chemotherapy in patients with advanced breast cancer in Western Europe

8,511, P = .012) relative to OAAs. CONCLUSIONS PP treatment was associated with significantly lower total health care costs attributable to reduced inpatient admissions compared to OAAs. Higher mental health intensive case management participation among PP users may have contributed to the differences observed.

Characteristics and outcomes of ALK+ non‐small cell lung cancer patients in Korea

PURPOSE This study evaluated clinical outcomes and health care resource utilization associated with nonmedical switching from or discontinuation of anti-tumor necrosis factor (TNF) therapies in US clinical practice. METHODS Responding physicians extracted data from the medical charts of patients with Crohns disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, or psoriatic arthritis who achieved response on an anti-TNF therapy. Physicians selected 2 cohorts of patients that were matched on diagnosis: patients who were switched/discontinued, for nonmedical reasons, from the anti-TNF therapy on which they achieved response (switchers/discontinuers), and patients who continued on their anti-TNF (continuers). Switchers/discontinuers were followed up for 12 months from the date of discontinuation (index date); continuers were followed up for 12 months from the date of an office visit within 2 months of the matched switcher/discontinuer׳s index date. Multivariate regression was used to compare disease flares, disease control, and health care resource utilization between cohorts, with adjustment for baseline characteristics. Subgroup analyses compared data from the continuer cohort to those from (1) patients who were switched to another biologic therapy and (2) patients who were switched to conventional therapy or discontinued from all therapy. FINDINGS A total of 377 matched pairs of continuers and switchers/discontinuers were analyzed (N = 754), with the latter cohort comprising 284 patients (73.3%) who were and 93 (24.7%) who did not switch to another treatment (biologic or conventional treatment) immediately after discontinuation. Switchers/discontinuers had more frequent flares than did continuers, across severity levels (adjusted incidence rate ratios = 1.67, 2.36, and 3.48 for mild, moderate, and severe flares, respectively; all, P < 0.05). Switchers/discontinuers had a lower rate of well-controlled disease symptoms (46.9% vs 88.1%; adjusted odds ratio = 0.11; P < 0.001). Switchers/discontinuers also had more frequent inpatient hospitalizations, emergency department visits, and outpatient visits (adjusted incidence rate ratios = 3.58, 5.73, and 1.12, respectively; all, P < 0.001). Findings from the subgroup analyses of data from the 183 patients who switched to a biologic therapy and 194 who switched to conventional therapy or discontinued from all therapy were largely consistent with the overall analysis. IMPLICATIONS In this study, switching/discontinuation from an anti-TNF therapy for nonmedical reasons was associated with significantly worse clinical outcomes and increased health care resource utilization-factors that should be considered when developing treatment algorithms.

Out-of-Pocket Medical Costs and Third-Party Healthcare Costs for Children With Down Syndrome

Abstract Objective: This study aimed to compare time on treatment (TOT) among patients treated with everolimus and chemotherapy, two commonly used treatments for hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC). Methods: Postmenopausal women with HR+/HER2- mBC who initiated ≥1 new line of therapy for mBC during 20 July 2012–31 March 2014 after a non-steroidal aromatase inhibitor were identified from MarketScan and PharMetrics databases (2002Q1–2014Q2) using a claims-based algorithm. Patients were classified into treatment groups by regimen and line of therapy, and were followed until discontinuation of therapy, end of insurance eligibility, or data cut-off (30 June 2014). Discontinuation was defined as a treatment gap of ≥60 days; patients who did not discontinue were censored at the end of follow-up. TOT was compared between everolimus, chemotherapy, and capecitabine monotherapy using Kaplan–Meier analyses and multivariable Cox models adjusting for line of therapy, age, insurance, de novo mBC diagnosis, prior use of chemotherapy for mBC, sites of metastases, and Charlson comorbidity index. Results: Across the first four lines of therapies for mBC, a total of 940 everolimus, 3410 chemotherapy, and 721 capecitabine monotherapy regimens were included. Based on the different lines of therapies, the median TOT ranged from 5.5 to 7.2 months for everolimus, 4.3 to 4.7 months for chemotherapy, and 3.5 to 6.0 months for capecitabine monotherapy. Pooling all lines of therapies, everolimus was associated with significantly longer TOT compared to chemotherapy (multivariable-adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.62–0.76) or capecitabine monotherapy (multivariable-adjusted HR = 0.73, 95% CI: 0.64–0.83). Longer TOT was consistently observed for everolimus for each line of therapy. Limitations: Proxies used for identifying HR + /HER2- mBC and treatment line, lack of certain clinical factors in claims data, generalizability limited to commercially insured patients in the US. Conclusions: This study found that HR+/HER2- mBC patients receiving everolimus experienced significantly longer TOT than those receiving chemotherapy overall or capecitabine monotherapy.

Treatment patterns and factors associated with the use of everolimus among post-menopausal women with HR+/HER2- metastatic breast cancer: a retrospective US claims study

Abstract Background: Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL) both have consistent expression of CD30, a cytokine receptor that is expressed by activated T and B cells but is largely absent from normal tissue. Methods: A literature search was conducted via PubMed, Google Scholar, and UpToDate to identify relevant peer-reviewed original research or review articles on HL, sALCL, and CD30 targeted therapies. Results: These lymphomas are both more common among males, young adults and the elderly. Although many patients with HL and sALCL can achieve long-term remission after standard first-line therapy, up to a third of these patients are refractory to or relapse after initial therapy. Among these relapsed/refractory patients, many experience disease progression and/or death despite subsequent treatment, and treatment-related adverse events and mortality are not uncommon. To address the need for safer and more effective therapies for these relapsed/refractory patients, researchers have developed therapies that specifically target CD30-expressing cells. Brentuximab vedotin, an antibody–drug conjugate that selectively delivers a toxic microtubule-disrupting agent to malignant cells with CD30 expression, is the first such therapy to be approved in the US and Europe. In clinical trials, brentuximab vedotin has demonstrated efficacy and safety in patients with HL after failure of autologous stem cell transplantation (ASCT), or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and in patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. Conclusion: HL and sALCL are both CD30+ lymphomas, and therapies like brentuximab vedotin that target cells expressing CD30 hold promise for the treatment of these diseases.