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Objectives: This study aimed to demonstrate enhanced survival extrapolation methods using electronic health record-derived real-world data (RWD).Methods: The study population included patients diagnosed of ER+/HER2- metastatic breast cancer who started first-line treatment with anastrozole or letrozole between November 18, 2014, and November 18, 2015. Two patient cohorts were constructed: a clinical trial cohort from digitized MONARCH-3 clinical trial results and a RWD cohort from a deidentified electronic health record-derived database. RWD patients were weighted to trial baseline covariate distributions. Standard parametric approaches were applied to trial data and a "best-fit" model was selected. We demonstrate traditional and enhanced hybrid (pooling with weighted RWD at start, 75%, or end of trial) extrapolation approaches.Results: Observed and estimated 5-year progression-free survival (PFS) rates in extrapolating the trial control arm (n = 165) were comparable across all methods. Compared with the observed 5-year mean PFS in the RWD cohort (n = 118) of 20.4 months (95% confidence interval [CI] 16.9-23.8), there was some variation among studied methods. Best-fit standard parametric model (log-normal) had 5-year mean PFS of 21.3 months (95% CI 18.2-24.9), and for the hybrid methods in order of estimate conservativeness was start of trial (20.8 months; 95% CI 18.5-23.2), 75% of trial (21.3 months; 95% CI 18.1-24.5), and end of trial (21.8 months; 95% CI 18.8-25.2).Conclusions: Our study leverages RWD to enhance long-term survival extrapolation. Future use cases should include applying patient eligibility criteria, weighting on baseline characteristics, and choice of time window to add RWD to trial data. [ABSTRACT FROM AUTHOR]

Objective: We investigated the quantification of the response shift-adjusted treatment effect on quality-of-life (QOL) data in a randomized controlled trial of taxane versus S-1 for patients with metastatic breast cancer (SELECT-BC).Methods: This study was a secondary data analysis of a previously published trial. The response shift-adjusted treatment effect on health-related QOL (HRQOL) data measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was estimated using structural equation modeling techniques in addition to quantifying the "true" treatment effect. Measurement invariances in the values of the common factor loadings, intercepts, and residual variances between before treatment and at the 3-, 6-, and 12-month visits were considered the response shift effects.Results: In the taxane group, we observed positive recalibration effects for role functioning and positive reprioritization and negative recalibration effects for emotional functioning. The observed change of -4.56 for role functioning comprised +2.26 response shifts and -6.82 "true" change. The observed change of +9.41 for emotional functioning comprised +12.43 response shifts and -1.17 "true" change. In the S-1 group, we observed positive reprioritization and negative recalibration effects for emotional functioning and positive reprioritization effects for social functioning. The observed change of +10.54 for emotional functioning comprised +10.07 response shifts and +0.47 "true" change. The observed change of +2.43 for social functioning comprised +3.50 response shifts and -1.07 "true" change.Conclusion: Detailed analysis of the response shift effects will improve the evaluation reliability of observed HRQOL data during clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: Background : Ouwens et al. and Jansen have presented methods for (network) meta-analysis of survival data by using a multidimensional treatment effect as an alternative to the synthesis of constant hazards ratios, which allow for a better fit to the data and the expected survival of competing interventions for cost-effectiveness analysis. However, results may be sensitive to the assumed underlying survival function. Objective: To estimate the expected progression-free survival (PFS) for fulvestrant 500 mg versus alternative hormonal therapies for postmenopausal women with advanced breast cancer who relapsed previously by means of a network meta-analysis of currently available randomized controlled trials using alternative underlying survival functions. Methods: Eleven randomized controlled trials were included that evaluated fulvestrant 500 mg (n = 3), fulvestrant 250 mg (n = 5), fulvestrant 250 mg loading dose (n = 3), anastrozole 1 mg (n = 3), megestrol acetate (n = 4), letrozole 2.5 mg (n = 3), letrozole 0.5 mg (n = 3), and exemestane (n = 2). PFS percentages and numbers at risk were derived from Kaplan-Meier curves and combined by means of Bayesian network meta-analysis on the basis of the difference in the shape and scale parameters of the Weibull, log-normal, and log-logistic parametric survival functions. Results: The log-normal distribution provided the best fit, suggesting that the proportional hazard assumption was not valid. Based on the difference in expected PFS, it was found that fulvestrant 500 mg is more efficacious than fulvestrant 250 mg, megestrol acetate, and anastrozole (−5.73 months; 95% credible interval [CrI]−10.67,−1.67). Expected PFS for fulvestrant 500 mg ranged from 10.87 (95% CrI 9.21, 13.07) to 17.02 (95% CrI 13.33, 22.02) months for the Weibull versus log-logistic distribution. Conclusions: Fulvestrant 500 mg is expected to be more efficacious than fulvestrant 250 mg, megestrol acetate, and anastrozole 1 mg and at least as efficacious as exemestane and letrozole 2.5 mg in terms of PFS among postmenopausal women with advanced breast cancer after failure on endocrine therapy. The findings were not sensitive to the distribution, although the expected PFS varied substantially, emphasizing the importance of performing sensitivity analyses. [Copyright &y& Elsevier]

To evaluate benefits and challenges when implementing a novel mobile application ("app") within a prospective site-based multicenter study. Although mHealth applications allow for the collection of large amounts of data, analysis and summarization can be complicated, particularly in handling missing data. [Extracted from the article]

The objective of this study is to describe treatment patterns and prognostic factors of patients with advanced or metastatic HR+/HER2- breast cancer in Argentina. Methods Patients with HR+/HER2- locally advanced or metastatic breast cancer who received endocrine therapy (ET), chemotherapy (CHT) or radiotherapy from 2013 to 2018 were selected from the Instituto de Especialidades Médicas clinical database, which includes individuals covered by the social security. In those patients who started treatment before 2016, first line therapies were CDK4/6 inhibitors 4%, ET 62% and CHT 61% (39% of those who received two or more treatments). [Extracted from the article]

Under current reimbursement (CR) practice, although an add-on medicine in a combination therapy may produce marginal value in terms of health gain, the original therapy may also share in the reward for this additional value. Our aim was to evaluate the impact of MVBR model on effective price (EP) and value-based price (VBP) of an add-on therapy, as compared to CR model. Conclusions If pertuzumab as the add-on therapy in combination were to fully capture the marginal value, its EP and VBP would be significantly higher compared to those prices under the CR model. [Extracted from the article]

There is scarce data on the effect of concordance to the National Comprehensive Cancer Network (NCCN) treatment guidelines on clinical and economic outcomes among patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The objective of this study was to examine the effect of guideline-concordant treatment among elderly women with HER2-negative MBC on all-cause mortality, breast cancer-specific mortality, and Medicare costs. In adjusted analyses, we found that women who did not receive guideline-concordant treatment had significantly higher hazards of all-cause mortality (hazard ratio (HR)=2.143, p<0.001) and breast cancer-specific mortality (HR=1.989, p<0.001) than those who received guideline-concordant treatment. [Extracted from the article]

The advent of trastuzumab biological medicine has opened up new strides in treatment of HER2-positive (HER2+) breast cancer. Methods Cost minimization analysis was used with cost components including drug cost, labor cost, other costs related to route of use, non-medical direct and indirect costs. [Extracted from the article]

This exploratory study uses random forest (RF) to predict optimal treatment resulting in longest overall survival (OS) for patients initiating first or second line of therapy (LOT) for HR+/HER2- metastatic breast cancer (mBC) to build understanding of how machine learning may help inform clinical decision-making. Individual regimens were grouped into hierarchy regimen classes with top three included in this analysis (CDK4/6 inhibitor-based therapy, endocrine therapy and chemotherapy). [Extracted from the article]

METASTATIC BREAST CANCER (ABC): A BRAZILIAN PRIVATE PAYER PERSPECTIVE To evaluate the cost-effectiveness of ribociclib compared to palbociclib, both in combination with letrozole, in first-line treatment of postmenopausal women HR+/HER2- ABC from the perspective of the Brazilian Private Health System (BPHS). From the BPHS perspective, ribociclib plus letrozole is a cost-saving alternative to palbociclib plus letrozole for the first-line treatment of postmenopausal women HR+/HER2- ABC. [Extracted from the article]