Valerie Koo

Everolimus-Based Therapy versus Chemotherapy among Patients with HR+/HER2− Metastatic Breast Cancer: Comparative Effectiveness from a Chart Review Study

Objective. To compare the real-world effectiveness of everolimus-based therapy and chemotherapy in postmenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative (HR+/HER2−) metastatic breast cancer (mBC). Methods. This retrospective chart review examined a nationwide sample of postmenopausal HR+/HER2− mBC women in community-based oncology practices. Patients received everolimus-based therapy or chemotherapy for mBC between 07/01/2012 and 04/15/2013, after failure of a non-steroidal aromatase inhibitor. Overall survival (OS), progression-free survival (PFS), and time on treatment (TOT) were compared using Kaplan-Meier analysis and Cox proportional hazards models adjusting for line of therapy and baseline characteristics. Results. 234 and 137 patients received everolimus-based therapy and chemotherapy. Patients treated with everolimus-based therapy tended to have less aggressive mBC than patients treated with chemotherapy. Multivariate-adjusted Cox models showed that everolimus-based therapy was associated with significantly longer OS [hazard ratio (HR) = 0.37, 95% confidence interval (CI): 0.22–0.63], PFS (HR = 0.70, 95% CI = 0.50–0.97), and TOT (HR = 0.34, 95% CI: 0.25–0.45) than chemotherapy. Adjusted comparative effectiveness results were generally consistent across lines of therapy. Conclusion. In this retrospective chart review of postmenopausal HR+/HER2− mBC patients, treatment with everolimus-based therapy was associated with longer OS, PFS, and TOT than chemotherapy.

Comparative effectiveness of everolimus-based therapy versus endocrine monotherapy among postmenopausal women with HR+/HER2− metastatic breast cancer: a retrospective chart review in community oncology practices in the US

Abstract Background: Everolimus-based therapy and endocrine monotherapy are used among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2−) metastatic breast cancer (mBC) whose disease progressed or recurred on a non-steroidal aromatase inhibitor (NSAI). However, limited evidence exists regarding the real-world comparative effectiveness of these agents. Methods: This retrospective chart review examined postmenopausal HR+/HER2− mBC patients in community-based oncology practices who received everolimus-based therapy or endocrine monotherapy (index therapy) as any line of therapy for mBC between 1 July 2012 and 15 April 2013 after NSAI failure. Time on treatment (TOT), progression-free survival (PFS), and time to chemotherapy (TTC) from index therapy initiation were compared using Kaplan–Meier analyses and Cox proportional hazards models adjusting for baseline characteristics. Results: A total of 243 and 270 patients received everolimus-based therapy or endocrine monotherapy in a quota-based sample. Patients treated with everolimus-based therapy had a higher proportion of visceral metastases, high tumor burden, and use of prior chemotherapies for mBC. After adjusting for baseline characteristics, everolimus-based therapy was associated with significantly longer TOT (HR = 0.67, 95% CI: 0.51–0.87) and PFS (HR = 0.75, 95% CI: 0.57–0.98) than endocrine monotherapy. No significant difference was found between everolimus-based therapy and endocrine monotherapy in TTC (HR = 0.81, 95% CI: 0.52–1.27). Results stratified by line of therapy were generally consistent with the overall results. Limitations: Limitations include recall and information bias with potentially absent or erroneous chart data, unobserved factors due to non-randomization, inability to measure outcome assessments paired with measuring outcomes prior to exposures, and potential patient selection bias associated with chart review. Conclusions: Among a nationwide sample of postmenopausal HR+/HER2− mBC patients treated in community oncology settings, treatment with everolimus-based therapy was associated with significantly longer TOT and PFS compared to endocrine monotherapy.

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

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.

Real-world effectiveness of everolimus-based therapy versus endocrine monotherapy and chemotherapy in patients of HR+/HER2- breast cancer with liver metastasis in the USA

Objective: This study investigated the comparative effectiveness of everolimus-based therapy (EVE) versus endocrine monotherapy (ET) and chemotherapy (CT) in the treatment of hormone-receptor-positive human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients with liver metastasis. Methods: Medical charts of patients treated by community oncologists were examined. Eligible patients included postmenopausal women with HR+/HER2- mBC with liver metastasis who received EVE, ET or CT between 1 July 2012 and 15 April 2013 after non-steroidal aromatase inhibitor use. Time on treatment (TOT) and progression-free survival (PFS) were compared between EVE and ET or CT using Kaplan–Meier analyses and Cox proportional hazards models. Results: Among the 202 patients in the study, 82 received EVE, 49 ET, and 71 CT. After adjusting for baseline characteristics, EVE was associated with significantly longer TOT than ET (hazard ratio [HR]: 0.49; 95% CI: 0.28 – 0.86) or CT (HR: 0.35; 95% CI: 0.22 – 0.55), and significantly longer PFS than ET (HR: 0.48; 95% CI: 0.27 – 0.87). PFS was not significantly different with EVE versus CT (HR: 0.76; 95% CI: 0.44 – 1.32). Conclusions: EVE had significantly longer TOT and PFS than ET and longer TOT than CT among postmenopausal HR+/HER2- mBC patients with liver metastasis.

A risk score for fluconazole failure among patients with candidemia

ABSTRACT This study aimed to develop a prediction model to identify patients with candidemia who were at high risk of failing fluconazole treatment. Adult patients in the United States with candidemia who received fluconazole during hospitalization were selected from the Cerner Health Facts Hospital Database (04/2004 to 03/2013). Fluconazole failure was defined as switching/adding another antifungal, positive Candida culture ≥10 days after fluconazole initiation, or death during hospitalization. Patients were randomized into modeling and validation samples. Using the modeling sample, a regression analysis of least absolute shrinkage and selection operator was used to select risk predictors of fluconazole failure (demographics, Candida species, initiation of fluconazole before positive culture and after admission, and comorbidities, procedures, and treatments during the 6 months before admission and fluconazole initiation). The prediction model was evaluated using the validation sample. We found that of 987 identified patients (average age of 61 years, 51% male, 72% Caucasian), 49% failed and 51% did not fail fluconazole treatment. Of those who failed, 70% switched or added another antifungal, 21% had a second positive Candida test, and 42% died during hospitalization. Nine risk factors were included in the prediction model: days to start fluconazole after admission, Candida glabrata or Candida krusei infection, hematological malignancy, venous thromboembolism (VTE), enteral nutrition, use of nonoperative intubation/irrigation, and other antifungal use. All but VTE were associated with a higher risk of failure. The models c-statistic was 0.65, with a Hosmer-Lemeshow test P value of 0.23. In summary, this prediction model identified patients with a high risk of fluconazole failure, illustrating the potential value and feasibility of personalizing candidemia treatment.

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 Objective: To assess the real-world use of everolimus in the treatment of 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 a new therapy for mBC between 20 July 2012 and 31 March 2014 after a non-steroidal-aromatase-inhibitor were identified from two commercial claims databases. Multivariate logistic regressions were used to identify factors associated with everolimus use versus endocrine-monotherapy or chemotherapy. Dosing patterns and adherence to everolimus were summarized. Results: A total of 940 everolimus, 6,134 endocrine-monotherapy, and 3,410 chemotherapy regimens were included across patients’ first four lines of therapy. Patients with bone and visceral metastases were more likely to use everolimus versus endocrine-monotherapy. Patients with more comorbidities, visceral or central-nervous-system metastases, and prior chemotherapy use for mBC were less likely to use everolimus versus chemotherapy. Approximately 80% of patients initiated everolimus at label-recommended-dose of 10 mg daily; 60–70% of patients had a medical possession ratio >0.8 to everolimus, and consistently high adherence was observed across lines of therapy. Conclusions: For HR+/HER2- mBC, patients treated with everolimus had more severe disease than patients treated with endocrine-monotherapy but less severe disease than patients treated with chemotherapy. Most patients used everolimus according to label-recommended dose and adherence was high across lines of therapy.

Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer.

AIMS Assessing real-world effectiveness of everolimus-based therapy (EVE) versus fulvestrant monotherapy (FUL) among postmenopausal women with hormone receptor-positive (HR(+))/HER2(-) metastatic breast cancer (mBC) after progression on nonsteroidal aromatase inhibitor (NSAI). DATA & METHODS Medical charts of community-based patients who received EVE or FUL for mBC after NSAI were examined. Progression-free survival (PFS), time on treatment and time to chemotherapy were compared using Kaplan-Meier curves and Cox proportional hazards models adjusting for line of therapy and patient characteristics. RESULTS & CONCLUSION 192 patients received EVE and 156 FUL. After adjusting for patient characteristics, EVE was associated with significantly longer PFS than FUL (hazard ratio: 0.71; p = 0.045). EVE was associated with better PFS than FUL among NSAI-refractory postmenopausal HR(+)/HER2(-) mBC patients.

Real-world persistence with fingolimod for the treatment of multiple sclerosis: A systematic review and meta-analysis

OBJECTIVE To systematically review reports of fingolimod persistence in the treatment of relapsing-remitting multiple sclerosis (RRMS) across data sources and practice settings, and to develop a consensus estimate of the 1-year real-world persistence rate. METHODS A systematic literature review was conducted (MEDLINE, EMBASE, and abstracts from selected conferences [2013-2015]) to identify observational studies reporting 1-year fingolimod persistence among adult patients with RRMS (sample size ≥50). A random-effects meta-analysis was performed to estimate a synthesized 1-year persistence rate and to assess heterogeneity across studies. RESULTS Of 527 publications identified, 25 real-world studies reporting 1-year fingolimod persistence rates were included. The studies included patients from different data sources (e.g., administrative claims, electronic medical records, or registries), used different definitions of persistence (e.g., based on prescriptions refills, patient report, or prescription orders), and spanned multiple geographic regions. Reported 1-year persistence rates ranged from 72%-100%, and exhibited statistical evidence of heterogeneity (I2 = 93% of the variability due to heterogeneity across studies). The consensus estimate of the 1-year persistence rate was 82% (95% confidence interval: 79%-85%). CONCLUSIONS Across heterogeneous study designs and patient populations found in real-world studies, the consensus 1-year fingolimod persistence rate exceeded 80%, consistent with persistence rates identified in the recently-completed trial, PREFERMS.

Abstract P4-22-19: Time on treatment of everolimus versus endocrine monotherapy or chemotherapy for early-line treatment of HR+/HER2- metastatic breast cancer: A retrospective chart review study in the US

Background: Among postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC) whose disease progressed on a non-steroidal aromatase inhibitor (NSAI), everolimus-based therapy (EVE), different endocrine monotherapies (ET mono), and chemotherapies (CT) are commonly used. Time on treatment is an outcome primarily determined by a therapy9s combined efficacy and safety profile. This study assessed the real-world time on treatment (TOT) among patients receiving these treatments in early-line (i.e., 1st and 2nd) settings. Methods: A nationwide sample of postmenopausal HR+/HER2- mBC patients treated by community oncologists in the US was included in this retrospective chart review. Eligible patients for this study were required to fail NSAI and then receive EVE, ET mono or CT (index therapy) as an early-line therapy for mBC between July 1, 2012 and April 15, 2013. TOT was measured from index therapy initiation to physician-reported treatment discontinuation and compared among treatment groups using Kaplan-Meier analyses with log-rank tests and Cox proportional hazards models adjusting for the line of therapy and baseline characteristics including recurrent or de novo disease status, age, race, insurance type, Charlson comorbidity index, sites of metastases (e.g., bone, any other visceral site), ECOG performance status, previous CT treatment in the mBC setting, and duration from the initiation of the last adjuvant ET to mBC diagnosis. Results: A total of 145 patients treated with EVE, 217 patients treated with ET mono, and 102 patients treated with CT were included in the analysis. Baseline characteristics among the three treatment groups were similar, although EVE-treated patients had higher burden of metastases relative to ET mono-treated patients, but lower burden relative to CT-treated patients. TOT was longer among EVE-treated patients than ET mono- and CT- treated patients (log-rank tests: p=0.01 and p Conclusions: This real-world US chart review study of postmenopausal women with HR+/HER2- mBC showed that patients receiving EVE in line 1 or 2 experienced significantly longer TOT than those receiving ET mono or CT. Citation Format: Li N, Ohashi E, Koo V, Xie J, Hao Y, Tang DH. Time on treatment of everolimus versus endocrine monotherapy or chemotherapy for early-line treatment of HR+/HER2- metastatic breast cancer: A retrospective chart review study in the US [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-19.

Comparison of medical costs and healthcare resource utilization of post-menopausal women with HR+/HER2- metastatic breast cancer receiving everolimus-based therapy or chemotherapy: a retrospective claims database analysis.

Abstract Objective: To analyze medical costs and healthcare resource utilization (HRU) associated with everolimus-based therapy or chemotherapy among post-menopausal women with hormone-receptor-positive, human-epidermal-growth-factor-receptor-2-negative (HR+/HER2−) metastatic breast cancer (mBC). Methods: Patients with HR+/HER2− mBC who discontinued a non-steroidal aromatase inhibitor and began a new line of treatment with everolimus-based therapy or chemotherapy (index therapy/index date) between July 20, 2012 and April 30, 2014 were identified from two large claims databases. All-cause, BC-related, and adverse event (AE)-related medical costs (in 2014 USD) and all-cause HRU per patient per month (PPPM) were analyzed for both treatment groups across patients’ first four lines of therapies for mBC. Adjusted differences in costs and HRU between the everolimus and chemotherapy treatment group were estimated pooling all lines and using multivariable generalized linear models, accounting for difference in patient characteristics. Results: A total of 3298 patients were included: 902 everolimus-treated patients and 2636 chemotherapy-treated patients. Compared to chemotherapy, everolimus was associated with significantly lower all-cause (adjusted mean difference =