Association between trajectories of adherence to endocrine therapy and risk of treated breast cancer recurrence among US nonmetastatic breast cancer survivors.

BACKGROUND: Endocrine therapy is the mainstay treatment for breast cancer (BC) to reduce BC recurrence risk. During the first year of endocrine therapy use, nearly 30% of BC survivors are nonadherent, which may increase BC recurrence risk. This study is to examine the association between endocrine therapy adherence trajectories and BC recurrence risk in nonmetastatic BC survivors. METHODS: This retrospective cohort study included Medicare beneficiaries in the United States (US) with incident nonmetastatic BC followed by endocrine therapy initiation in 2010-2019 US Surveillance, Epidemiology, and End Results linked Medicare data. We calculated monthly fill-based proportion of days covered in the first year of endocrine therapy. We applied group-based trajectory models to identify distinct endocrine therapy adherence patterns. After the end of the first-year endocrine therapy trajectory measurement period, we estimated the risk of time to first treated BC recurrence within 4 years using Cox proportional hazards models. RESULTS: We identified 5 trajectories of adherence to endocrine therapy in BC Stages 0-I subgroup (n = 28,042) and in Stages II-III subgroup (n = 7781). A trajectory of discontinuation before 6 months accounted for 7.0% in Stages 0-I and 5.8% in Stages II-III subgroups, and this trajectory was associated with an increased treated BC recurrence risk compared to nearly perfect adherence (Stages 0-I: adjusted hazard [aHR] = 1.84, 95% CI = 1.46-2.33; Stages II-III: aHR = 1.38, 95% CI = 1.07-1.77). CONCLUSIONS: Nearly 7% of BC survivors who discontinued before completing 6 months of treatment was associated with an increased treated BC recurrence risk compared to those with nearly perfect adherence among Medicare nonmetastatic BC survivors.

Association between trajectories of prescription opioid use and risk of opioid use disorder and overdose among US nonmetastatic breast cancer survivors.

PURPOSE: To examine the association between prescription opioid use trajectories and risk of opioid use disorder (OUD) or overdose among nonmetastatic breast cancer survivors by treatment type. METHODS: This retrospective cohort study included female nonmetastatic breast cancer survivors with at least 1 opioid prescription fill in 2010-2019 Surveillance, Epidemiology and End Results linked Medicare data. Opioid mean daily morphine milligram equivalents (MME) calculated within 1.5 years after initiating active breast cancer therapy. Group-based trajectory models identified distinct opioid use trajectory patterns. Risk of time to first OUD/overdose event within 1 year after the trajectory period was calculated for distinct trajectory groups using Cox proportional hazards models. Analyses were stratified by treatment type. RESULTS: Four opioid use trajectories were identified for each treatment group. For 38,030 survivors with systemic endocrine therapy, 3 trajectories were associated with increased OUD/overdose risk compared with early discontinuation: minimal dose (< 5 MME; adjusted hazard ratio [aHR] = 1.73 [95% CI 1.43-2.09]), very low dose (5-25 MME; 2.67 [2.05-3.48]), and moderate dose (51-90 MME; 6.20 [4.69-8.19]). For 9477 survivors with adjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 7.33 [95% CI 2.52-21.31]) compared with early discontinuation. For 3513 survivors with neoadjuvant chemotherapy, the differences in OUD/OD risks across the 4 trajectories were not significant. CONCLUSIONS: Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, low-dose or moderate-dose opioid use were associated with six- to sevenfold higher OUD/overdose risk. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral).

Trends, characteristics, race, and ethnicity associated with nonadherence to antidepressants among breast cancer survivors with depression.

BACKGROUND: Breast cancer is the most diagnosed cancer in the United States, and half of breast cancer survivors experience major depressive disorders (hereafter depression). Healthcare Effectiveness Data and Information Set (HEDIS) quality measures evaluating depression treatment practices recommend uninterrupted antidepressant treatment for 3 months in the acute phase and 3 months in the continuation phase for the general population. However, little is known about the extent of and trends in antidepressant nonadherence among breast cancer survivors with depression, which may impact adherence to breast cancer treatment, potentially leading to breast cancer recurrence and other adverse outcomes. OBJECTIVE: To examine the trends and characteristics associated with antidepressant nonadherence among breast cancer survivors with depression in the United States. METHODS: We conducted cross-sectional analyses of Surveillance, Epidemiology, and End Results linked with Medicare data (2010-2019) for women with breast cancer and depression who newly initiated antidepressant use. Using HEDIS measures of nonadherence (ie, antidepressant prescription coverage ≤84 days of the 114-day acute phase or ≤180 days of the 231-day continuation phase), we calculated the annual crude prevalence of antidepressant nonadherence and examined trends using unadjusted logistic regression. Multivariable logistic regression identified characteristics associated with antidepressant nonadherence. RESULTS: Among 9,452 eligible breast cancer survivors with depression (aged ≥65 years = 84% and White race = 82%), the crude prevalence of antidepressant nonadherence decreased from 2010 to 2019 for both the acute (49% to 40%; Ptrend<0.001) and continuation (67% to 57%; Ptrend<0.001) phases. Factors significantly associated with higher odds of antidepressant nonadherence in both the acute and continuation phases included Black race (odds ratios [ORs] [95% CI] for the acute/continuation phases: 2.0 [1.7-2.4]/2.0 [1.7-2.3]) and Hispanic ethnicity (1.5 [1.1-1.9]/2.2 [1.6-2.9]) compared with White race; receiving the first antidepressant from an oncologist vs a psychiatrist (1.4 [1.1-1.8]/1.6 [1.2-2.0]); and using antidepressants not recommended for older adults by the Beers criteria (2.2 [1.6-2.9]/2.0 [1.4-2.7]). Factors associated with lower odds of antidepressant nonadherence in both phases included receiving lymph node dissection (0.7 [0.5-0.9]/0.7 [0.5-0.9]), receiving endocrine therapy (0.9 [0.8-0.9]/0.8 [0.7-0.9]), having a higher National Cancer Institute comorbid index (0.8 [0.7-0.8]/0.9 [0.8-0.9]), having a follow-up visit with a psychiatrist (0.9 [0.8-0.9]/0.9 [0.8-0.9]), and switching to different antidepressants (0.7 [0.6-0.8]/0.7 [0.7-0.8]). CONCLUSIONS: Despite antidepressant nonadherence prevalence decreasing from 2010 to 2019, over half of breast cancer survivors with depression and Medicare were nonadherent in the continuation phase. Patients with identified nonadherence risk factors may benefit from close monitoring and targeted interventions. DISCLOSURES: Wei-Hsuan Lo-Ciganic reported grants from the National Institute on Drug Abuse (R01DA044985 and R01DA050676), the National Institute on Aging (R21AG060308), the National Institute of Mental Health (R01MH121907), Merck Sharp & Dohme, Bristol Myers Squibb, the Richard King Mellon Foundation at the University of Pittsburgh, the Clinical and Translational Science Institute of the University of Florida, the Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation, and the US Department of Veterans Affairs outside the submitted work; in addition, Wei-Hsuan Lo-Ciganic has a patent pending for U1195.70174US00. Haesuk Park reported grants from Bristol Myers Squibb/Pfizer Alliance American Thrombosis Investigator Initiated Research Program (ARISTA-USA) outside the submitted work. Juan M. Hincapie-Castillo reported grants from Merck outside the submitted work. Debbie Wilson reported grants from the National Institute on Drug Abuse, the National Institute on Aging, Merck Sharp & Dohme, and Bristol Myers Squibb outside the submitted work; and serving as an editorial board member for the Journal of Pharmacy Technology. Ching-Yuan Chang's contributions to this manuscript were made while at the University of Florida College of Pharmacy. Ching-Yuan Chang is currently employed by Vertex Pharmaceuticals, Inc. Vertex did not fund or have any involvement in this study or publication. Vakaramoko Diaby is currently employed by Otsuka, Inc. Otsuka did not fund or have any involvement in this study or publication. No other disclosures were reported.

An Umbrella Review of the Cost Effectiveness of Human Papillomavirus Vaccines.

BACKGROUND AND OBJECTIVES: Although many systematic reviews for the human papillomavirus vaccines cost effectiveness have been published, they vary in perspectives, methods, and quality. We aimed to condense systematically such evidence to facilitate locating, processing, and learning, not only about the consensus of findings but also how models were built and their evolution over time and across settings. METHODS: We conducted an umbrella review of cost-effectiveness studies for human papillomavirus vaccines using three databases (PubMed, Embase, and Cochrane). Based on their objectives, we classified studies into three groups (human papillomavirus vaccines cost effectiveness, model characteristics, and all-type vaccines, including human papillomavirus vaccines). We used the AMTAR2 to assess the quality of the studies. Additionally, we provided a summary of study findings, discussions, and evidence gaps in the literature. RESULTS: Though most studies were critically low quality and had a low quality of reporting, the human papillomavirus vaccine was consistently cost effective in young girls and men who have sex with men. Stratified analyses by rated quality did not change the results. The quality assessment of the reviews did not necessarily reflect the quality assessment of underlying studies. The human papillomavirus vaccine models became more complex over time, capturing more realistic disease transmission with different human papillomavirus strains and herd immunities. CONCLUSIONS: Additional evidence is needed for vulnerable populations (e.g., childhood cancer survivors) who are at high risk for human papillomavirus vaccine-related cancers and, therefore, may be more cost effective when receiving human papillomavirus vaccines. Quantifying human papillomavirus vaccine cost effectiveness via meta-analyses is feasible if investigators can increase the homogeneity of their populations.

Comparative cost-effectiveness of radiotherapy among older women with hormone receptor positive early-stage breast cancer.

OBJECTIVE: The aim was to examine the real-world cost-effectiveness of breast-conserving surgery (BCS) plus hormonal therapy with radiotherapy, compared to hormonal therapy alone among women 66 and older with hormone receptor positive early-stage breast cancer in the United States (US). METHODS: This study was conducted from a U.S. Centers for Medicare and Medicaid Services perspective and an eight-year time horizon. Both costs (2020 US$) and health utilities (quality-adjusted life years, QALYs) were obtained from retrospective studies using the SEER linked with Medicare and Medicare Health Outcomes Survey, respectively. The incremental cost-effectiveness ratio (ICER) of the addition of radiotherapy to hormonal therapy versus hormonal therapy alone after BCS was estimated by an unbiased doubly robust estimator. Sensitivity analyses were conducted through bootstrapping to estimate credible intervals. RESULTS: The addition of radiotherapy to hormonal therapy after BCS yielded the highest clinical benefits (2.66 QALYs) and costs ($19,424.27) compared to its hormonal therapy alone after BCS (0.77 QALYS; $2,028.58). The ICER was estimated to be $9,174.94/QALY. Sensitivity analyses did not change the direction of the findings. CONCLUSIONS: The results implicated that the combination of radiotherapy and hormonal therapy is cost-effective in the US.

Health Care Utilization and Costs Associated With Systemic First-Line Metastatic Melanoma Therapies in the United States.

PURPOSE: US Food and Drug Administration approvals of immune checkpoint inhibitors and targeted therapies revolutionized the treatment of metastatic melanoma. Our aim was to assess health care resource utilization and costs for patients with metastatic melanoma treated with systemic therapies in first line between January 2012 and December 2017. METHODS: We conducted a retrospective cohort study of patients with metastatic melanoma using MarketScan data. We included patients diagnosed with melanoma and secondary malignant neoplasm who used pembrolizumab, nivolumab, ipilimumab, ipilimumab plus nivolumab, BRAF-inhibitor (BRAF-i) plus MEK inhibitor (MEK-i), BRAF-i or MEK-i monotherapy, or chemotherapy in first line. We compared health care utilization and costs per patient per month (PPPM) using two-part and generalized linear models. RESULTS: We identified 1,870 patients, including 185 pembrolizumab, 103 nivolumab, 689 ipilimumab, 185 nivolumab plus ipilimumab, 214 BRAF-i plus MEK-i, 240 BRAF-i or MEK-i monotherapy, and 254 chemotherapy users. Highest PPPM rates of hospitalizations, emergency room visits, and outpatient visits were observed in patients with ipilimumab plus nivolumab therapy (adjusted difference v pembrolizumab [aDiff], 0.18, 0.12, and 0.88, respectively; all P < .001). Ipilimumab monotherapy users (aDiff, 0.07 and 0.93; all P < .001) and chemotherapy users (aDiff, 0.10 and 2.63; all P < .001) showed higher PPPM rates of hospitalizations and outpatient visits compared with pembrolizumab users, respectively. Utilization rates in nivolumab, BRAF-i plus MEK-i, and BRAF-i or MEK-i groups were similar to the pembrolizumab group. Highest PPPM total costs and drug-related costs were observed in the ipilimumab group ($80,139 US dollars [USD] and $70,051 USD; all P < .001), followed by the ipilimumab plus nivolumab ($71,689 USD and $56,217 USD; all P < .001) and the BRAF-i plus MEK-i group ($31,184 USD and $19,648 USD; all P < .001). PPPM costs in the nivolumab group were similar to the pembrolizumab group. CONCLUSION: Significant differences in health care resource utilization and costs were found across first-line metastatic melanoma regimens. Utilization rates were highest in patients using ipilimumab-containing therapies. High drug costs constituted a major fraction of total PPPM health care costs.

Incorporating health equity into value assessment: frameworks, promising alternatives, and future directions.

Exploring methods that value diverse perspectives is critical to better understand the value of health equity in value assessment frameworks. In this paper, we examined emerging value assessment frameworks in the United States and present examples where evidence on outcomes and preferences for value do not take into consideration diverse perspectives. We identify possible solutions to improve existing value assessment methods and illustrate-using a hypothetical shared decision-making case study-an alternative to current value-assessment frameworks, "equitable multicriteria decision analysis," which could be implemented in the context of the value-based assessment of prevention choices for women at high risk of developing breast cancer. These proposed alternatives and solutions can be used by researchers and decision makers to incorporate health equity into value assessment. DISCLOSURES: No funding was received for this study. The authors have no conflicts of interest to report.

Cost-effectiveness and drug wastage of immunotherapeutic agents for hematologic malignancies: a systematic review.

Introduction: Novel immunotherapeutic agents (e.g. monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engagers) as treatment options for hematologic malignancies continue to emerge. These agents have been used as the standard of care in specific disease states and are associated with high costs. Value assessment of these therapies is of critical importance for coverage and reimbursement decision-making.Areas covered: We identified 15 immunotherapeutic agents through the U.S. FDA approvals for hematologic malignancies until 2018 and systematically reviewed related cost-effectiveness studies. Additionally, we examined whether drug wastage was accounted for in these studies.Expert opinion: We reviewed 51 studies for 14 identified immunotherapeutic agents that met the inclusion criteria for this systematic review. Three studies were observational-based, one study was model-based and incorporated observational data. The remaining studies were model-based with the majority of the model parameters extracted from randomized control trials (RCTs). Among 43 model-based economic evaluations, 13 studies accounted for drug wastage. Most of the studies showed favorable incremental cost-effectiveness ratios of immunotherapeutic agents-containing regimens when compared with no immunotherapeutic agents-containing regimens. Alemtuzumab, brentuximab vedotin, and daratumumab were not considered cost-effective across all the studies. Further investigations are warranted to establish the value of recent immunotherapeutic agents for hematologic malignancies.

Evaluation of statin discontinuation stratified by primary versus secondary prevention following bariatric surgery: a retrospective cohort study.

BACKGROUND: Bariatric surgery leads to an improvement in hyperlipidemia and a subsequent decline in the use of hyperlipidemia-related medications, including statins. In patients with a history of atherosclerotic cardiovascular disease (ASCVD), it is recommended to continue statins; however, it is unknown whether there is a differential risk for statin discontinuation in patients with and without a history of ASCVD. OBJECTIVES: To estimate the rates and factors associated with statin discontinuation following bariatric surgery. SETTING: Large U.S. administrative claims database of privately insured beneficiaries, January 2005 through December 2017. METHODS: We identified patients aged ≥19 years who were statin users at the time of bariatric surgery. Patients were stratified into primary prevention and secondary prevention (patients with a history of ASCVD) groups. Time to statin discontinuation was defined as the first 90-day gap after exhausting the last day's supply of the last statin prescription. Factors associated with statin discontinuation were assessed using the Cox proportional hazards regression model. RESULTS: We identified 19,332 statin users at the time of bariatric surgery, of whom 84% (16,221) used statins for primary prevention. At 6 months, 62% and 53% of patients in the primary and the secondary prevention treatment groups, respectively, discontinued statin use. Patients in the primary prevention treatment group were 18% more likely to discontinue statin therapy compared with the patients in the secondary prevention treatment group (hazard ratio, 1.18; 95% confidence interval, 1.13-1.24) according to a multivariable analysis. CONCLUSIONS: Our findings suggest that the rate of discontinuation of statin therapy after bariatric surgery was more pronounced in the primary versus secondary prevention treatment group.

Cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases: an overview of systematic reviews.

Introduction: Treatment of human epithelial growth factor receptor 2 (HER2)-positive breast cancer has rapidly evolved over the past decades with the addition of trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1). These treatments have dramatically impacted the survival of HER2-positive metastatic breast cancer (mBC) patients. Nonetheless, these agents are associated with high price tags, begging the question, 'Are treatments for HER2-positive metastatic breast cancer and associated metastases cost-effective'?Areas covered: We examine evidence on the cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases through a review of systematic reviews on the topic. Additionally, we discuss the implications of our findings and provide recommendations for future directions in the assessment of the cost-effectiveness of targeted directed agents for HER2-positive mBC.Expert opinion: Heterogeneous evidence from cost-effectiveness studies on the use of targeted directed agents for HER2-positive mBC across the world caution against cross-country comparisons of the value of such treatments. It also militates in favor of the production and use of cost-effectiveness analyses for local rather than global decision-making, thus ensuring that economic evaluations reflect the needs of local decision-makers and populations for which they are devised.

Timing, Costs, and Survival Outcome of Specialty Palliative Care in Medicare Beneficiaries With Metastatic Non-Small-Cell Lung Cancer.

PURPOSE: ASCO recommends early integration of palliative care in treating patients diagnosed with metastatic lung cancer. Our study sought to examine utilization of timely specialty palliative care (SPC) and its association with survival and cost outcomes in patients diagnosed with metastatic non-small-cell lung cancer (NSCLC). METHODS: The 2001-2015 SEER-Medicare data were used to determine the baseline characteristics and outcomes of 79,253 patients with metastatic NSCLC. The predictors of early SPC use were examined using logistic regression. Mean and adjusted total and SPC-related costs were calculated using generalized linear regression. We used Cox regression model to determine the survival outcomes by SPC service settings. All statistical tests were two sided. RESULTS: The time from cancer diagnosis to the first SPC use has reduced significantly, from 13.7 weeks in 2001 to 8.3 weeks in 2015 (P < .001). SPC use was associated with lower health care costs compared with those who had no SPC, from -$3,180 in 2011 (P < .001) to -$1,285 in 2015 (P = .059). Outpatient SPC use was associated with improved survival compared with patients who received SPC in other settings (hazard ratio, 0.83; 95% CI, 0.79 to 0.88; P < .001). CONCLUSION: Patients diagnosed with metastatic NSCLC now have more timely SPC service utilization, which was demonstrated to be a cost-saving treatment. Strategies to improve outpatient palliative care use might be associated with longer survival in patients with metastatic NSCLC.

Real-World Clinical and Economic Outcomes Associated with Palbociclib for HR-Positive/HER2 Negative Metastatic Breast Cancer: A Commentary.

Despite the achieved advancement in pharmacological cancer treatments, the majority of postmenopausal women with hormone receptor-positive metastatic breast cancer (mBC) will experience disease progression. Research into alternative therapies with improved efficacy and reduced side effects has led to the development of a new class of oral anticancer medications, the cyclin-dependent kinase (CDK) 4/6 inhibitors, which include palbociclib, ribociclib, and abemaciclib. Nonetheless, there is growing evidence that the effectiveness of oral anticancer medications is sub-optimal, being influenced by low adherence, sociodemographic factors, and adverse effect profiles. In addition, there is a disconnect between the high price tags of CDK 4/6 inhibitors and their observed effectiveness, raising questions about their value. Currently, the existing knowledge base on the effectiveness and cost-effectiveness of newer oral anticancer medications in understudied populations with possible health disparities is scant. This commentary discusses what is known about palbociclib's clinical effectiveness, safety, and adherence and suggests the need for further studies of real-world effectiveness and cost-effectiveness to help establish the value of newer oncologic drugs, such as palbociclib. DISCLOSURES: No funding supported the writing of this article. The authors have nothing to disclose.

Cost-Effectiveness of Subsequent Whole-Brain Radiotherapy or Hippocampal-Avoidant Whole-Brain Radiotherapy Versus Stereotactic Radiosurgery or Surgery Alone for Treatment of Melanoma Brain Metastases.

BACKGROUND: A randomized phase III trial comparing whole-brain radiotherapy (WBRT) to observation following definitive local treatment of intracranial melanoma metastases with neurosurgery and/or stereotactic surgery (SRS) is underway. OBJECTIVE: We sought to assess the pre-trial cost-effectiveness of WBRT, hippocampal-avoidant WBRT (HA-WBRT), and observation (SRS or surgery alone) for this population to guide trial data collection efforts and reduce decision uncertainty. METHODS: A time-dependent Markov model followed patients treated with neurosurgery or SRS who received subsequent WBRT, HA-WBRT or observation over a 5-year time horizon. Model inputs were sourced from published literature and results tested for robustness using probabilistic sensitivity analysis. Value of information (VOI) analysis was undertaken to guide data collection for the randomized trial. RESULTS: Over 5 years, the WBRT strategy produced 1.74 QALYs (2.38 life-years) at a mean cost of $40,128 (costs in 2017 Australian dollars); HA-WBRT produced 1.88 QALYs (2.38 life-years) and cost $42,977; and SRS/surgery alone produced 1.65 QALYs (2.13 life-years) at a cost of $46,281. Probabilistic sensitivity analysis showed HA-WBRT was the preferred strategy in 77% of simulations. Cost-effectiveness results were most sensitive to utilities of the controlled-disease health state in the WBRT group, and costs of HA-WBRT. The EVPI for a randomized trial was estimated at $6,888 per person. CONCLUSIONS: HA-WBRT may be cost-effective for the treatment of melanoma brain metastases. The results predicted in our model can be validated with prospective trial data when available.

Cost-Effectiveness Analysis of Adjuvant Neratinib Following Trastuzumab in Early-Stage HER2-Positive Breast Cancer.

DISCLOSURES: No funding supported the writing of this letter. The authors report no conflicts of interest related to the subject of this letter.

Dataset used in the economic evaluation trastuzumab-based regimens for HER-2 positive metastatic breast cancer patients in the Taiwanese healthcare setting.

The present data article aims to describe the input parameters for a Markov model assessing the cost-effectiveness of four treatment sequences for patients with HER-2 positive metastatic breast cancer. The model input parameters include costs for physician visits, drugs, adverse event management, computed tomography (CT) scan, laboratory tests, echocardiogram, utilities, disutilities as well as the shape and scale parameters of a log-logistic distribution used for the transition probabilities.

A cost-effectiveness analysis of trastuzumab-containing treatment sequences for HER-2 positive metastatic breast cancer patients in Taiwan.

OBJECTIVE: Treatment options for HER-2-positive metastatic breast cancer (mBC) patients have expanded markedly since trastuzumab approval in 1998. Several other regimens are now available, including pertuzumab plus trastuzumab plus docetaxel, T-DM1, capecitabine plus lapatinib, and trastuzumab plus lapatinib. This study assesses the cost-effectiveness of four treatment sequences for HER-2-positive mBC according to the Taiwanese National Health Insurance Administration (TNHIA). METHODS: Costs (U.S. Dollars) and effectiveness (quality-adjusted life years) of four treatment sequences for HER-2-positive mBC patients were examined using a Markov model over a lifetime horizon. Transition probabilities, disease progression, and probability of adverse events and survival were derived from clinical trial data. Costs and health utilities were estimated from TNHIA, Taipei Medical University Hospital, and the literature. Deterministic, probabilistic sensitivity analyses and a scenario analysis examined parameter uncertainty and accounted for drug wastage in dosage and cost calculations. RESULTS: Sequence 3 (1st line: trastuzumab plus docetaxel; 2nd line: T-DM1; 3rd line: trastuzumab plus lapatinib) was the most cost-effective sequence followed by sequence 1 (1st line: pertuzumab plus trastuzumab plus docetaxel; 2nd line: T-DM1; 3rd line: capecitabine plus lapatinib), and sequence 4 (1st line: trastuzumab plus docetaxel; 2nd line: trastuzumab plus lapatinib; 3rd line: trastuzumab plus capecitabine), respectively. The model was sensitive to costs and transition probabilities, but not particularly sensitive to the wastage assumption. CONCLUSIONS: From the perspective of the TNHIA, trastuzumab plus docetaxel as 1st line followed by T-DM1 and trastuzumab plus lapatinib as 2nd and 3rd line represents the most cost-effective strategy among the four sequences considered for treating HER-2-positive mBC patients.

Using time series analysis to forecast the health-related quality of life of post-menopausal women with non-metastatic ER+ breast cancer: A tutorial and case study.

BACKGROUND: Time series models are widely used forecasting techniques in health care for long time series and are typically built in commercial statistical packages. However, for short time series data, such as health-related quality of life (HRQoL), guidance on how to select and use appropriate time series models is lacking. This tutorial provides a step-by-step guide adopting a time series analysis framework for HRQoL forecasting. OBJECTIVE: We walk through a case study examining the forecasting of the effects of adjuvant endocrine therapy on the HRQoL of post-menopausal women with non-metastatic ER + breast cancer using data from the HRQoL sub-protocol of the Tamoxifen arm of the Arimidex, tamoxifen, alone or in combination (ATAC) trial. METHODS: The forecasting of HRQoL consists of four steps: 1) data extraction and accuracy check, 2) forecasting horizon definition and identification of data pattern, 3) forecasting model identification and fitting using five forecasting approaches appropriate for short time series ((i) double exponential smoothing, (ii) double moving average, (iii) fuzzy forecasting, (iv) grey forecasting, and (v) Volterra series), 4) forecasting model selection. A user-friendly visual basic for applications (VBA) Excel add-in is made available to interested users to facilitate the application of the tutorial. RESULTS: The Grey method and Volterra series appeared to be good candidates to forecast the effects of adjuvant endocrine therapy on the HRQoL of post-menopausal women with non-metastatic ER + breast cancer enrolled in the ATAC trial. CONCLUSION: It is feasible to forecast the effects of treatments on HRQOL even when the time series is short.

Examining factors associated with adherence to hormonal therapy in breast cancer patients.

BACKGROUD: Breast cancer is a rampant disease and is highly prevalent among women in the United States. Two out of three breast cancers are hormone receptor positive and hormonal therapies (Tamoxifen and Aromatase Inhibitors) are used to treat this type of breast cancer. However, adherence to these efficacious therapies is relatively low. PURPOSE: The aim of this study was to identify factors that are associated with adherence to hormonal therapy among breast cancer patients, and the extent to which they influence adherence, by looking at data from a nationally representative database. METHODS: A retrospective cross-sectional study was conducted using Medical Expenditure Panel Survey (MEPS) for 2011-2015. Individuals ≥18 years diagnosed with breast cancer utilizing Tamoxifen and Aromatase inhibitors were identified. The Proportion of Days Covered (PDC) adherence measure was used to classify individuals as adherent (PDC≥80%) or non-adherent (PDC<80%). Multivariable logistic regression was used to determine factors associated with adherence to hormonal therapy. RESULTS: Out of the 354 breast cancer respondents utilizing hormonal therapy, 194 (54.8%) were adherent and 160 (45.20%) were non-adherent. From 2011 through 2015, an increase in the usage of hormonal therapy was observed. Individuals having at least a high school diploma or General Equivalency Diploma (GED) had 2.795 (1.081, 6.941) times the odds of being adherent when compared to those who did not have a high school diploma or GED. Race, insurance status, marital status, poverty level, class of drug (aromatase inhibitor/tamoxifen), age, comorbidities, out-of-pocket costs and region were not significantly associated with adherence to hormonal therapy among breast cancer patients. CONCLUSIONS: This study found an association between an individual's level of education and adherence to hormonal therapy among breast cancer patients. These results can be used to help optimize allocation of resources to promote knowledge designed to increase the adherence of breast cancer patients to hormonal therapy.

Comparative effectiveness of radiotherapy for early-stage hormone receptor-positive breast cancer in elderly women using real-world data.

BACKGROUND: Radiotherapy is the recommended treatment after breast-conserving surgery (BCS) for early-stage breast cancer (BC). However, there is no clear evidence whether radiotherapy after BCS improves the survival of elderly women diagnosed with early-stage hormone receptor-positive (HR+) BC. The aim of this study was to investigate the survival benefit associated with radiotherapy plus hormonal therapy vs hormonal therapy alone after BCS for early-stage HR+ BC patients. METHODS: Using the Surveillance, Epidemiology, and End Results linked with Medicare data, we identified elderly (65 years and older) women diagnosed with early-stage HR+ BC (2006-2011) who received hormonal therapy with or without radiotherapy after BCS. A log-rank test, Cox proportional hazards models, and propensity score matching were used to estimate the overall survival (OS) benefit associated with radiotherapy after BCS. RESULTS: Of the 5688 patients, there were 303 deaths from any cause. One hundred and eighty-five (61%) of these deaths occurred in the hormonal therapy group, and 118 (39%) deaths occurred in the radiotherapy plus hormonal therapy group. The mean survival time in the radiotherapy plus hormonal therapy group was 5.32 ± 1.86 years compared with 4.92 ± 1.86 years in the hormonal therapy group. Based on the adjusted and propensity score matching analysis, patients in the adjuvant radiotherapy group had a lower risk of death compared with those who did not receive radiotherapy. Radiotherapy plus hormonal therapy decreased the risk of death by 32%. The effect estimates were similar in the adjusted and matched cohorts. CONCLUSIONS: Radiotherapy plus hormonal therapy resulted in a significant improvement in the OS of elderly women diagnosed with HR+ BC.

An Evaluation of the Cost-effectiveness of Comprehensive MTM Integrated with Point-of-Care Phenotypic and Genetic Testing for U.S. Elderly Patients After Percutaneous Coronary Intervention.

BACKGROUND: Poor health outcomes after percutaneous coronary intervention (PCI) in elderly patients is an area of concern among policymakers and administrators. In an effort to determine the best strategy to improve outcomes among elderly patients who underwent PCI, several studies have evaluated the cost-effectiveness of genotype-guided antiplatelet therapy compared with universal use of any one of the antiplatelet drugs indicated for patients with acute coronary syndrome (ACS) who underwent PCI. The results have either been in favor of genotype-guided antiplatelet therapy or universal use of ticagrelor. However, no study has yet evaluated the cost-effectiveness of pharmacist-provided face-to-face medication therapy management (MTM) combined with point-of-care genotype-guided antiplatelet therapy (POCP) when compared with universal use of ticagrelor or clopidogrel for the elderly after PCI. OBJECTIVE: To evaluate the cost-effectiveness of a pharmacist integration of MTM with POCP (MTM-POCP) when compared with universal use of ticagrelor or clopidogrel combined with MTM (MTM-ticagrelor or MTM-clopidogrel). METHODS: We conducted a cost-effectiveness analysis from the perspective of the U.S. health care system. A hybrid model, consisting of a 1-year decision tree and a 20-year Markov model, was used to simulate a cohort of elderly patients (aged at least 65 years) with ACS who underwent PCI. Treatment strategies available to patients were POCP, POCP-MTM, MTM-clopidogrel, or MTM-ticagrelor. Data used to populate the model were obtained from the PLATO trial and other published studies. Outcome measures were costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained. A deterministic and probabilistic sensitivity analysis was conducted to account for the joint uncertainty around the key parameters of the model. Finally, a benchmark willingness to pay of $50,000-200,000 was considered. RESULTS: The use of PCOP (with dual antiplatelet therapy) resulted in 5.29 QALYs, at a cost of $50,207. MTM-clopidogrel resulted in 5.34 QALYs, at a cost of $50,011. The use of POCP-MTM resulted in 5.36 QALYs, at a cost of $50,270. Finally, MTM-ticagrelor resulted in 5.42 QALYs, at a cost of $53,346. MTM-ticagrelor was found to be cost-effective compared with MTM-clopidogrel or MTM-POCP, irrespective of the willingness to pay. The deterministic and probabilistic sensitivity analyses confirmed the robustness of the base-case analysis. CONCLUSIONS: The combination of MTM-ticagrelor was cost-effective when compared with MTM-POCP or MTM-clopidogrel. The transitional probabilities, however, were mostly based on published studies. Analysis based on a prospective randomized clinical study, comparing all the treatment strategies included in this study, is warranted to confirm our findings. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to declare. Study concept and design were contributed by Okere and Diaby. Ezendu took the lead in data collection, along with Okere. Data interpretation was performed by all the authors. The manuscript was written by Okere, Diaby, and Berthe and revised by Okere and Diaby.