Yanni Hao

Treatment patterns and duration in post-menopausal women with HR+/HER2− metastatic breast cancer in the US: a retrospective chart review in community oncology practices (2004–2010)

Abstract Background: Clinical guidelines prefer endocrine therapy (ET) as initial treatment for post-menopausal women with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2−) metastatic breast cancer (mBC). Chemotherapy (CT) should be reserved for patients who develop symptomatic visceral disease or have no clinical benefit after three sequential ET regimens. It is unclear if real-world clinical practice reflects these guidelines. Objective: To describe treatment patterns and treatment durations by lines of therapy for ET and CT among post-menopausal HR+/HER2− mBC patients. Methods: Charts were reviewed from a network of community-based oncology practices of eligible patients who had progressed after initiating adjuvant or first-line treatment for mBC between 1 January 2004 and 30 September 2010. Extracted chart data included demographics, treatment histories, and outcomes. Treatment duration was estimated using Kaplan–Meier estimators. Results: A total of 144 patients were studied. Patients received a median of two lines of ET, and <10% had three or more lines of ET before receiving CT. From first line to second line, the median treatment duration was 11.6 to 4.9 months for ET overall; 13.8 to 10.5 months for anastrozole; 18.6 to 7.0 months for letrozole; and 5.1 to 2.9 months for fulvestrant. For CT, the median duration was 5.1 months in the first line and 3.7 months and below in subsequent lines. Conclusion: During the study period (1 January 2004 – 30 September 2012), most patients received <3 lines of ET before receiving CT. The drop in median duration of ET from first to second line suggests that single agent ETs might not be as effective beyond the first line. A key limitation of this study was the small sample size. In addition, more research is needed to further investigate the short treatment duration of fulvestrant across early lines of therapy (which could indicate lack of efficacy).

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 (HRu2009=u20090.67, 95% CI: 0.51–0.87) and PFS (HRu2009=u20090.75, 95% CI: 0.57–0.98) than endocrine monotherapy. No significant difference was found between everolimus-based therapy and endocrine monotherapy in TTC (HRu2009=u20090.81, 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.

Healthcare Resource Use and Expenditures among Metastatic Breast Cancer Patients Treated with HER2-Targeted Agents

Objective. To compare healthcare utilization (HCU) and costs of women newly diagnosed with metastatic breast cancer (mBC) by receipt of HER2-targeted agents (H2T) and among H2T subgroups. Methods. Adult women newly diagnosed with mBC (index date) during 2008–2012 were followed until enrollment end or inpatient death. Study cohorts were antineoplastic ± H2Ts, and no treatment; and subgroups of H2T patients stratified by receipt of hormonal therapy (HT+/HT−), by de novo versus recurrent disease status, and by age group. All-cause (ALL) and breast cancer related (BCR) HCU and costs (in 2012 dollars) were estimated using a generalized linear model. Results. Of 18,059 women, 14.6% were H2T users 71.1% nonusers, and 14.3% untreated. No treatment patients had the highest ALL and BCR inpatient HCU, and ALL emergency room HCU. H2Ts users had the highest ALL and BCR office visits, lab and diagnostic radiology, radiation treatments, other outpatient services, and prescription antineoplastics. Adjusted ALL and BCR costs were the highest for H2T users and, in H2T subgroups, higher for HT—versus HT+ and de novo versus recurrent, and declined with older age. Conclusions. Receipt of H2Ts was associated with greater levels of ALL and BCR HCU and costs. H2T subgroups of HT−, de novo, and younger age had higher HCU and costs, possibly indicating more aggressive treatments.

Patient-Reported Outcomes in Metastatic Breast Cancer: A Review of Industry-Sponsored Clinical Trials

Introduction Patient-reported outcome (PRO) measures serve to capture vital patient information not otherwise obtained by primary study endpoints. This paper examines how PROs are utilized as endpoints in industry-sponsored metastatic breast cancer clinical trials. Methods A search was conducted in the clinicaltrials.gov web site for trials involving common treatments for metastatic breast cancer. Thirty-eight clinical trials were identified which included a PRO endpoint in the study, and data were extracted and summarized. Results Overall, 17 unique PRO questionnaires and 14 concepts of measurement were identified as secondary or exploratory endpoints. The Functional Assessment of Cancer Therapy—Breast was the most frequently utilized questionnaire, commonly implemented to assess quality of life. The EORTC QLQ-C30 was also frequently used to measure quality of life or pain. Conclusion This review shares insights into the role of PROs in trials for metastatic breast cancer from which treatment developers and other stakeholders can enhance successful implementation of the patient voice into future trials.

Clinical outcomes among HR+/HER2- metastatic breast cancer patients with multiple metastatic sites: a chart review study in the US.

BackgroundHormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2−) is the most common type of metastatic breast cancer (mBC). While mBC patients generally have poor prognosis with limited progression-free survival (PFS) and overall survival (OS), those with multiple metastatic sites may have even worse clinical outcomes due to multiple organ involvement. This study aimed to compare clinical outcomes including PFS, time on treatment (TOT), and OS between HR+/HER2− mBC patients with multiple metastases versus those with a single metastasis in a real-world clinical setting.MethodsThis was a retrospective chart review study of postmenopausal HR+/HER2− mBC women who had failed a non-steroidal aromatase inhibitor in the adjuvant or metastatic setting and initiated a new treatment for mBC between 07/01/2012 and 04/15/2013. Patients were classified to one of two study groups (multiple metastases or single metastasis) based on the number of non-lymph-node metastases at the initiation of the new treatment. PFS, TOT and OS were compared between the two groups using Kaplan–Meier analyses and multivariable Cox proportional hazard models adjusting for patient disease and treatment characteristics. Separate Cox models were conducted including models with an interaction term between line of therapy and study group to assess the impact of multiple metastases on clinical outcomes across different lines of therapy.ResultsA total of 699 patient charts were collected, including 291 patients with multiple metastases and 408 single metastasis patients. Worse performance status and a higher proportion of prior chemotherapy for mBC were observed among patients with multiple metastases. Overall, patients with multiple metastases had significantly shorter PFS [adjusted hazard ratio (HR)xa0=xa01.55, 95xa0% confidence interval (CI) 1.21–1.98], TOT (adjusted HRxa0=xa01.33, 95xa0% CI 1.05–1.67), and OS (adjusted HRxa0=xa01.77, 95xa0% CI 1.15–2.74) than single metastasis patients. Similar outcomes were observed in each line of therapy.ConclusionsAmong HR+/HER2− mBC patients, patients with multiple metastases had significantly shorter PFS, TOT, and OS than single metastasis patients, highlighting the substantial clinical burden and unmet need for more efficacious treatments for the former group of patients.

Physician experiences and preferences in the treatment of HR+/HER2− metastatic breast cancer in the United States: a physician survey

Sequential endocrine therapy (ET) is recommended for postmenopausal women with hormone receptor‐positive (HR+)/human epidermal growth factor receptor 2‐negative (HER2−) metastatic breast cancer (mBC) and without visceral symptoms. Chemotherapy (CT) can be considered after sequential ETs, but is associated with adverse side effects. We assessed physicians preferences and self‐reported prescribing patterns for ET and CT in the treatment of HR+/HER2− mBC at community practices in the United States. Community‐based oncologists/hematologists from a nationwide online panel who treated postmenopausal women with HR+/HER2− mBC were invited to complete a survey, blinded to the identity of study sponsor. Treatment preferences were collected by treatment class of ET‐based regimens versus CT and by agent for postmenopausal HR+/HER2− mBC patients after prior nonsteroidal aromatase inhibitor use in the adjuvant or mBC setting. Among 213 physicians who completed the survey, 78% were male, 71% were based in small/intermediate practices (2–9 oncologists/subspecialists), 55% had >10 years of experience, and 58% referred to the National Comprehensive Cancer Network Guidelines when treating mBC. Among first‐line ETs, anastrozole was the most frequently used treatment (35%), followed by everolimus‐based (EVE, 34%) and fulvestrant‐based (FUL, 15%) therapy. After first‐line ET, the most preferred second‐ and third‐line treatments were ET monotherapy (48% and 39%), ET combination therapy (31% and 19%), and CT monotherapy (13% and 30%). Comparing EVE versus FUL, physicians preferred EVE in all lines but first line. Efficacy was the most important consideration for treatment choice. Physicians prescribed CT in early lines mainly because of visceral symptoms. This survey of treatment patterns for HR+/HER2− mBC in community practice suggested that after first‐line ET, ET mono‐ or combination therapy was commonly used for the second‐ and third‐line treatments and CT monotherapy for third‐ or later line treatments. CTs were used in early lines for patients with visceral symptoms.

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]u2009=u20090.69, 95% confidence interval [CI]: 0.62–0.76) or capecitabine monotherapy (multivariable-adjusted HRu2009=u20090.73, 95% CI: 0.64–0.83). Longer TOT was consistently observed for everolimus for each line of therapy. Limitations: Proxies used for identifying HRu2009+u2009/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.

Clinical Trial Patient-reported Outcomes Data: Going Beyond the Label in Oncology

PURPOSEnPatient-reported outcome (PRO) data are increasingly being implemented in oncology clinical trial research to evaluate treatment benefit, such as disease-related symptoms, treatment-related adverse events, and health-related quality of life impacts. However, only a small amount of PRO data collected is used to support labeling claims, leaving a substantial amount of data that could be shared by sponsors to further convey treatment benefit from the patient perspective.nnnMETHODSnThis paper describes how pharmaceutical sponsors can realize the value of PRO data derived from oncology trials with regard to the following stakeholders: payers, health care providers (HCPs), and patient advocacy groups. Further, ideas are presented for integrating PRO data and implementing PRO assessments within oncology, by stakeholder type. Finally, a summary is provided to describe how PRO data can benefit the patient by facilitating better, more symptom-focused care and enhancing treatment decisions.nnnFINDINGSnWith the goal of motivating further use of PRO assessments in oncology, we present examples of how payers utilize PRO data to inform reimbursement decisions (eg, PRO data inform decisions made by Germany׳s Institute for Quality and Efficiency in Health Care and the United Kingdom׳s National Institute for Health and Care Excellence); how communication of results with patient advocacy groups can lead to a better understanding of what is important to patients; and how HCPs can use PRO instruments to inform patient treatment decisions through real-world application.nnnIMPLICATIONSnIntegrating PRO data can enhance health care by allowing the patients voice to carry beyond regulatory decisions and into those made by payers and HCPs, which are crucial to quality care and assessing the value of care. Utilizing PRO assessments and communicating results to key stakeholders in the oncology space can allow sponsors to report treatment benefit and, more importantly, can provide valuable insight into the patient treatment experience.

Real-World Analysis of Medical Costs and Healthcare Resource Utilization in Elderly Women with HR+/HER2− Metastatic Breast Cancer Receiving Everolimus-Based Therapy or Chemotherapy

IntroductionThe objective of this study was to analyze medical costs and healthcare resource utilization (HRU) associated with everolimus-based therapy or chemotherapy among elderly women with hormone-receptor-positive, human-epidermal-growth-factor-receptor-2-negative (HR+/HER2−) metastatic breast cancer (mBC).MethodsElderly women (≥65xa0years) with HR+/HER2− mBC who failed a non-steroidal-aromatase-inhibitor and subsequently began a new line of treatment with everolimus-based therapy or chemotherapy for mBC (index therapy) during July 20, 2012 to March 31, 2014 were identified from two large commercial claims databases. All-cause, BC-, and adverse event (AE)-related medical costs (2014xa0USD), and all-cause and AE-related HRU per patient per month (PPPM) were compared between patients treated with everolimus-based therapy and chemotherapy across their first four lines of therapy for mBC. Adjusted costs and HRU differences were estimated by pooling all lines and using multivariable models adjusted for differences in patient characteristics.ResultsIn total, 925 elderly patients (mean age approximately 73xa0years) with HR+/HER2− mBC met the inclusion criteria; 230 received everolimus-based therapy (240 lines) and 737 received chemotherapy (939 lines). Compared with chemotherapy, everolimus-based therapy was associated with significantly lower total all-cause PPPM medical services costs (adjusted mean difference: