Adjuvant hormone strategies in postmenopausal women with breast cancer: An economic evaluation based on the EBCTCG meta-analyses

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6574-6574
Author(s):  
T. Younis ◽  
D. Rayson ◽  
C. Skedgel
Keyword(s):  
Breast Cancer ◽  
Economic Evaluation ◽  
Hormonal Treatment ◽  
Sensitivity Analyses ◽  
Collaborative Group ◽  
Generic Model ◽  
Primary Analysis ◽  
Meta Analyses ◽  
Very High ◽  
Hormonal Treatments

6574 Background: Meta-analyses conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) demonstrated significant improvements in breast cancer (BC) outcomes associated with tamoxifen (TAM) and/or aromatase inhibitor (AI) therapy. We conducted an economic evaluation, based on these meta-analyses, to examine the cost-effectiveness (CE) of adjuvant TAM, sequential TAM-AI and upfront AI in post menopausal (PM) women with BC. Methods: A generic model was developed to calculate cumulative costs and quality adjusted life year gains (QALYG) over 25-year horizon in hypothetical cohorts of PM women with BC undergoing 5-year treatment with TAM alone, upfront AI, or sequential TAM-AI. We examined different cohorts with varying 10-year baseline recurrence risk (RR) without adjuvant hormonal treatments to reflect the natural spectrum of breast cancer disease encountered (low = 25%; average = 38%; high = 50%; very high = 75%). The efficacy outcomes were derived from the EBCTCG meta-analyses, with 10-year duration of benefit assumed for all strategies. Costs and utilities were derived from the literature, and local resources. The analysis took a direct payer perspective and reports costs in 2008 Cdn$. Costs and benefits were discounted at 3%. CE was based on the $50,000/QALY gained threshold. Adverse events were not included in the primary analysis. Sensitivity analyses were conducted. Results: Adjuvant hormonal treatments with TAM and/or AI are CE strategies in PM women with BC. The costs and QALYG associated with hormonal treatments were dependent on the baseline RR: CE estimates were more favorable in cohorts with higher as opposed to lower RR. The baseline RR also influenced the choice of the optimal economic strategy. Upfront AI was associated with higher costs and more QALY gains compared to TAM-AI. CE however was favorable in patients with average to very high RR and unfavorable in patients with low RR. Conclusions: Adjuvant treatments with TAM and/or AI are associated with favorable CE in PM women with BC. The optimal CE strategies, however, are dependent on the baseline RR without hormonal treatment. A risk-tailored hormonal treatment choice could optimize the overall health system efficiency. [Table: see text]

Direct and indirect economic evaluation of upfront and sequential adjuvant treatment in postmenopausal women with breast cancer based on the BIG 1–98 trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6594-6594
Author(s):  
C. Skedgel ◽  
D. Rayson ◽  
T. Younis
Keyword(s):  
Breast Cancer ◽  
Economic Evaluation ◽  
Postmenopausal Women ◽  
Indirect Comparison ◽  
Cost Savings ◽  
Hormonal Treatment ◽  
Recurrence Risk ◽  
Quality Adjusted Life Year ◽  
Sensitivity Analyses ◽  
Carry Over

6594 Background: The monotherapy arms of the BIG 1–98 trial established the clinical superiority of upfront letrozole (LET) relative to tamoxifen alone (TAM) but direct comparison of sequential TAM-LET, LET-TAM and upfront LET did not establish a clinically superior strategy. We undertook an economic evaluation to identify an economically preferred strategy based on the relative cost-effectiveness (CE) of TAM, LET, TAM-LET, and LET-TAM in terms of cost per quality-adjusted life year gained (QALYG). Methods: A state-transition model was developed to calculate cumulative costs and QALYs over a 25yr horizon for hypothetical cohorts of postmenopausal women with HR+ breast cancer undergoing adjuvant hormonal treatment. As the sequential arms were not directly compared to TAM alone, it was not possible to directly compare all strategies. As such, the analysis conducted direct within-arm comparisons and an indirect between-arm comparison. DFS endpoints and relative DFS benefit were derived from the monotherapy and sequential arms of BIG 1–98. Adverse events were not included as these have not yet been reported. Sensitivity analyses were conducted for the key parameters and assumptions, including the baseline recurrence risk and the duration of carry-over benefit. Costs and utility weights were derived from the literature. The analysis took a Canadian direct payer perspective and drug costs were based on 2008 Canadian average wholesale prices. Costs and outcomes were discounted at 3%. Results: In the monotherapy arms LET had a CE of $16,650 relative to TAM. In the sequential arms LET-TAM had superior QALYGs and cost savings relative to LET and TAM-LET. In economic terms, LET-TAM dominated LET and TAM-LET. In the indirect comparison, LET-TAM dominated LET and TAM-LET and had superior QALYGs at increased cost relative to TAM for a CE of $178. Conclusions: Direct comparisons confirm the economic favourability of LET relative to TAM and establish the dominance of LET-TAM over LET and TAM-LET. These indirect comparisons support the strong economic favourability of LET-TAM relative to TAM in the indirect comparison. In the absence of superior clinical outcomes, economic evaluation is a useful in suggesting a preferred strategy. No significant financial relationships to disclose.

Meta-Analysis of Breast Cancer Outcomes in Adjuvant Trials of Aromatase Inhibitors Versus Tamoxifen

2010 ◽  
Vol 28 (3) ◽  
pp. 509-518 ◽  
Author(s):  
Mitch Dowsett ◽  
Jack Cuzick ◽  
Jim Ingle ◽  
Alan Coates ◽  
John Forbes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Cancer Mortality ◽  
Breast Cancer Mortality ◽  
Hormonal Treatment ◽  
Collaborative Group ◽  
Recurrence Rates ◽  
Term Survival ◽  
Meta Analyses

Purpose To conduct meta-analyses of randomized trials of aromatase inhibitors (AIs) compared with tamoxifen either as initial monotherapy (cohort 1) or after 2 to 3 years of tamoxifen (cohort 2). Materials and Methods Data submitted to the Early Breast Cancer Trialists' Collaborative Group were used in separate meta-analyses of two cohorts. Primary analyses involve postmenopausal women with tumors reported to be estrogen receptor positive. Log-rank P values are two-sided. Results Cohort 1 comprised 9,856 patients with a mean of 5.8 years of follow-up. At 5 years, AI therapy was associated with an absolute 2.9% (SE = 0.7%) decrease in recurrence (9.6% for AI v 12.6% for tamoxifen; 2P < .00001) and a nonsignificant absolute 1.1% (SE = 0.5%) decrease in breast cancer mortality (4.8% for AI v 5.9% for tamoxifen; 2P = .1). Cohort 2 comprised 9,015 patients with a mean of 3.9 years of follow-up. At 3 years from treatment divergence (ie, approximately 5 years after starting hormonal treatment), AI therapy was associated with an absolute 3.1% (SE = 0.6%) decrease in recurrence (5.0% for AI v 8.1% for tamoxifen since divergence; 2P < .00001) and an absolute 0.7% (SE = 0.3%) decrease in breast cancer mortality (1.7% for AI v 2.4% for tamoxifen since divergence; 2P = .02). There was no convincing heterogeneity in the proportional recurrence reduction with respect to age, nodal status, tumor grade, or progesterone receptor status and no indication of an increase in nonbreast deaths with AIs in either cohort. Conclusion AIs produce significantly lower recurrence rates compared with tamoxifen, either as initial monotherapy or after 2 to 3 years of tamoxifen. Additional follow-up will provide clearer information on long-term survival.

Randomized trial of text messaging (TM) to reduce early discontinuation of aromatase inhibitor (AI) therapy in women with breast cancer: SWOG S1105.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6516-6516 ◽  
Author(s):  
Dawn L. Hershman ◽  
Joseph M. Unger ◽  
Hillyer Grace ◽  
Anna Moseley ◽  
Kathryn B Arnold ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Trial ◽  
Text Messaging ◽  
Behavioral Interventions ◽  
Cox Regression ◽  
Sensitivity Analyses ◽  
Rank Test ◽  
Missed Appointments ◽  
Primary Analysis

6516 Background: Non-adherence to AI’s for breast cancer is common and increases risk of recurrence. Text messaging (TM) has been shown to increase adherence to medications for chronic conditions. We conducted a multicenter randomized trial to evaluate if TM reminders improve AI adherence. Methods: Patients taking an AI for ≥30 days and having ≥36 mos of planned therapy were eligible. Patients were randomly assigned 1:1 to receive either TM or NO-TM twice a week for 36 mos. Randomization was stratified by length of time on prior AI therapy ( < 12 (64%) vs. 12-24 mos (36%)) and AI class (anastrozole, letrozole, exemestane). Content themes of the 36 TMs focused on overcoming barriers to adherence. Patients were assessed for discontinuation of AIs every 3 mos for 36 mos. The primary outcome was time to non-adherence, where non-adherence was defined as urine AI metabolite assay results satisfying the following: < 10 [units], undetectable, or no submitted specimen. A stratified Log-rank test was conducted. Multiple sensitivity analyses were performed using Cox regression. Results: In total, 724 patients were registered between May, 2012 and September, 2013, among whom 696 (338/360 (93.9%) on TM and 338/364 (92.9%) on NO-TM) were eligible and adherent at baseline. Observed (time-independent) adherence at 36 mos was 55.4% for TM and 55.4% for NO-TM. The primary analysis showed no difference in time-to-adherence failure between patients on the TM and NO-TM arms (HR = 0.89, 95% CI:0.76,1.05 p = .18). An analysis of negative urine tests alone resulted in similar non-significant results. With missed appointments not counted as failures, time to self-reported discontinuation (89.6% vs. 89.7%; HR = 1.17, 95% CI:0.69-1.98, p = .57) and site reported discontinuation (78.1% vs. 81.1%; HR = 1.31, 95% CI:0.86-2.01, p = .21) were also similar between the 2 groups. Conclusions: As the first large long-term randomized trial of an intervention directed at improving AI adherence, we found high rates of AI discontinuation. Bi-weekly text reminders did not improve adherence to AIs compared to usual care. Improving long—term adherence will likely require sustained behavioral interventions and support. Clinical trial information: NCT01515800.

scholarly journals Breast cancer worry in higher risk women offered preventive therapy: a UK multicentre prospective study

2020 ◽  
Author(s):  
Kelly Lloyd ◽  
Louise Hall ◽  
Lucy Ziegler ◽  
Samuel Smith
Keyword(s):  
Breast Cancer ◽  
White Women ◽  
Preventive Therapy ◽  
Sensitivity Analyses ◽  
Cancer Worry ◽  
Clinical Factors ◽  
Primary Analysis ◽  
Increased Risk ◽  
The Relationship

Purpose: Women’s worry about developing breast cancer may influence their decision to use preventive therapy. However, the direction of this relationship has been questioned. We prospectively investigated the relationship between breast cancer worry and uptake of preventive therapy. The socio-demographic and clinical factors associated with high breast cancer worry were also investigated.Methods: Women at increased risk of developing breast cancer were recruited from clinics across England (n=408). Participants completed a survey on their breast cancer worry, socio-demographic and clinical factors. Uptake of tamoxifen was recorded at 3-months (n=258 women, 63.2%). Both primary and sensitivity analyses were conducted using different classifications of low, medium and high worry.Results: 39.5% of respondents reported medium breast cancer worry at baseline and 21.2% reported high worry. Ethnic minority women were more likely to report high worry than white women (OR=3.02, 95%CI=1.02, 8.91, p=0.046). Women educated below degree level were more likely to report high worry than those with higher education (OR=2.29, 95%CI=1.28, 4.09, p=0.005). No statistically significant association was observed between worry and uptake. In the primary analysis, fewer respondents with medium worry at baseline initiated tamoxifen (low worry=15.5%, medium=13.5%, high=15.7%). In the sensitivity analysis, participants with medium worry reported the highest uptake of tamoxifen (19.7%).Conclusions: No association was observed between worry and uptake, although the relationship was affected by the categorisation of worry. Standardised reporting of the classification of worry is warranted to allow transparent comparisons across cohorts.

scholarly journals Meta-Analysis of Proptosis Response in Thyroid Eye Disease: Efficacy of EUGOGO Recommended Treatment Regimen With IV Methylprednisolone

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A842-A842
Author(s):  
Raymond S Douglas ◽  
Ryan Batten ◽  
Rana A Qadeer ◽  
Chris Cameron
Keyword(s):  
Study Design ◽  
Observational Studies ◽  
Meta Analysis ◽  
Thyroid Eye Disease ◽  
Recommended Dose ◽  
Sensitivity Analyses ◽  
Controlled Study ◽  
Eye Disease ◽  
Primary Analysis ◽  
Meta Analyses

Abstract Background: The European Group on Graves’ Orbitopathy (EUGOGO) recommends intravenous methylprednisolone (IVMP) as the first line treatment for moderate-to-severe active thyroid eye disease (TED). While many studies with varying doses of IVMP have reported improvements in inflammation, via clinical activity score (CAS) reduction, the reported improvements in the major progressive outcome of TED, proptosis, vary widely. A reduction in proptosis of ≥2 millimeter (mm) is considered by clinicians and EUGOGO as clinically meaningful. A meta-analysis of existing literature on use of IVMP in TED management, specifically proptosis response, was conducted. Methods: PubMed and Embase were searched for relevant randomized controlled trials (RCTs) and observational studies that included patients with moderate-to-severe active TED receiving treatment with the EUGOGO recommended dose of IVMP (4.5-5g over 12 weeks) from the inception of the databases to date of search (October 2020); regular alerts were established to capture any recent studies. The outcome of interest was change from baseline to week 12 in proptosis in mms. Single-arm meta-analyses were conducted for IVMP using the DerSimonian-Laird random-effects models and forest plots were generated. Pooled means and corresponding 95% confidence intervals (CIs) were calculated. The primary analysis included all identified studies. Sensitivity analyses were conducted based on study design, study characteristics (smoking status), and methodologies (weighted Bayesian meta-analyses based on study design). Results: The search retrieved 12 studies (10 single-center, 8 RCTs, 4 observational studies: 7 from China, 4 from EU, 1 from Turkey), reporting proptosis for 498 patients that were used for the meta-analysis. No placebo-controlled study with the EUGOGO recommended dose of IVMP was found. All studies included patients who were 18 years or older with moderate-to-severe TED and most (n=11) studies included patients with CAS of ≥3. For studies that reported this data, the mean or median (if mean not reported) age ranged from 35 to 52 years and duration of TED symptoms ranged from 4 to 13.6 months. Treatment with IVMP resulted in a reduction of 0.94 mm (95% CI: -1.57 to -0.32) in proptosis from baseline to week 12. The results from the sensitivity analyses were aligned with those from the primary analysis. Conclusions: Among patients with moderate-to-severe TED, this meta-analysis found the EUGOGO-recommended dose of IVMP may result in modest, but not clinically meaningful, improvements in proptosis. However, these results should be interpreted with caution given the paucity of published data and the lack of risk/benefit analyses with glucocorticoid use as compared to the recently FDA-approved therapy, teprotumumab, for the treatment of TED.

scholarly journals How robust are findings of pairwise and network meta-analysis in the presence of missing participant outcome data?

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Loukia M. Spineli ◽  
Chrysostomos Kalyvas ◽  
Katerina Papadimitropoulou
Keyword(s):  
Sensitivity Analysis ◽  
Systematic Reviews ◽  
Statistical Significance ◽  
Empirical Studies ◽  
Outcome Data ◽  
Sensitivity Analyses ◽  
Logarithmic Scale ◽  
Primary Analysis ◽  
Current Sensitivity ◽  
Meta Analyses

Abstract Background To investigate the prevalence of robust conclusions in systematic reviews addressing missing (participant) outcome data via a novel framework of sensitivity analyses and examine the agreement with the current sensitivity analysis standards. Methods We performed an empirical study on systematic reviews with two or more interventions. Pairwise meta-analyses (PMA) and network meta-analyses (NMA) were identified from empirical studies on the reporting and handling of missing outcome data in systematic reviews. PMAs with at least three studies and NMAs with at least three interventions on one primary outcome were considered eligible. We applied Bayesian methods to obtain the summary effect estimates whilst modelling missing outcome data under the missing-at-random assumption and different assumptions about the missingness mechanism in the compared interventions. The odds ratio in the logarithmic scale was considered for the binary outcomes and the standardised mean difference for the continuous outcomes. We calculated the proportion of primary analyses with robust and frail conclusions, quantified by our proposed metric, the robustness index (RI), and current sensitivity analysis standards. Cohen’s kappa statistic was used to measure the agreement between the conclusions derived by the RI and the current sensitivity analysis standards. Results One hundred eight PMAs and 34 NMAs were considered. When studies with a substantial number of missing outcome data dominated the analyses, the number of frail conclusions increased. The RI indicated that 59% of the analyses failed to demonstrate robustness compared to 39% when the current sensitivity analysis standards were employed. Comparing the RI with the current sensitivity analysis standards revealed that two in five analyses yielded contradictory conclusions concerning the robustness of the primary analysis results. Conclusions Compared with the current sensitivity analysis standards, the RI offers an explicit definition of similar results and does not unduly rely on statistical significance. Hence, it may safeguard against possible spurious conclusions regarding the robustness of the primary analysis results.

scholarly journals A Network Meta-Analysis to Compare Effectiveness of Baricitinib and Other Treatments in Rheumatoid Arthritis Patients with Inadequate Response to Methotrexate

2020 ◽  
Vol 7 (1) ◽  
pp. 10-23
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Janus Kinase ◽  
Sensitivity Analyses ◽  
Baseline Risk ◽  
Inadequate Response ◽  
Primary Analysis ◽  
American College Of Rheumatology ◽  
Meta Analyses

Background/Objectives: This article compares the effectiveness of baricitinib (BARI) 4 mg (oral, Janus kinase [JAK] 1/2 inhibitor) versus other targeted synthetic/biologic disease-modifying antirheumatic drugs, in combination with methotrexate (MTX), in moderate-to-severe rheumatoid arthritis patients with inadequate response (IR) to MTX. Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of the interventions of interest. Bayesian network meta-analyses (NMA) were used to compare American College of Rheumatology (ACR) responses at 24 weeks. A series of prespecified sensitivity analyses addressed the potential impact of, among others, baseline risk, treatment effect modifiers, and trial design on treatment response. Results: Nineteen RCTs were included in the NMA (primary analysis). For ACR20, BARI 4 mg + MTX was found to be more effective than adalimumab (ADA) 40 mg + MTX (Odds Ratio [OR] 1.33), abatacept (ABA) 10 mg + MTX (IV/4 weeks) (OR 1.45), infliximab (IFX) 3 mg + MTX (IV/8 wks) (OR 1.63), and rituximab (RTX) 1000 mg + MTX (OR 1.63). No differences were found on ACR50. For ACR70, BARI 4 mg + MTX was more effective than ADA 40 mg + MTX (OR 1.37), ABA 10 mg + MTX (OR 1.86), and RTX 1000 mg + MTX (OR 2.26). Sensitivity analysis including 10 additional RCTs with up to 20% of patients with prior biologic use showed BARI 4 mg + MTX to be more effective than tocilizumab (TCZ) 8 mg + MTX on ACR20 (OR 1.44). Results for all sensitivity analyses were consistent with the direction and magnitude of the primary results. Key limitations include the time span in which trials were conducted (1999–2017), during which patient characteristics and treatment approaches might have changed. Conclusion: This NMA suggests that BARI 4 mg + MTX is an efficacious treatment option in the MTX-IR population as evidenced by the robustness of results.

Breast surgery

2016 ◽  
Keyword(s):  
Breast Cancer ◽  
Breast Surgery ◽  
The United States ◽  
Breast Cancer Surgery ◽  
Collaborative Group ◽  
High Quality ◽  
Cancer Trials ◽  
Dynamic Time ◽  
Meta Analyses ◽  
Based Medicine

Breast cancer trials started in the 1930s and have made major contributions to the field of evidence-based medicine and the management of breast cancer. In the United States, the National Surgical and Adjuvant Breast Project (NSABP), established in 1957, has been responsible for many pivotal breast cancer trials in breast cancer surgery, radiotherapy, chemotherapy, and hormone therapy. The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) started in 1985, with the aim of sharing data from high-quality randomized trials worldwide to promote high-quality meta-analyses. Increasingly, breast cancer is being recognized not as one single pathology, but as a disease with a biology and behaviour that is individual to each patient. This chapter discusses trials which have been pivotal in this dynamic time for breast cancer research and which have led the way in personalized therapies for cancer patients.

Inferring the Effects of Cancer Treatment: Divergent Results From Early Breast Cancer Trialists’ Collaborative Group Meta-Analyses of Randomized Trials and Observational Data From SEER Registries

2016 ◽  
Vol 34 (8) ◽  
pp. 803-809 ◽  
Author(s):  
Katherine E. Henson ◽  
Reshma Jagsi ◽  
David Cutter ◽  
Paul McGale ◽  
Carolyn Taylor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Observational Data ◽  
Early Breast Cancer ◽  
Rate Ratio ◽  
Randomized Trials ◽  
Breast Conserving Surgery ◽  
Collaborative Group ◽  
Node Positive Disease ◽  
Rate Ratios ◽  
Meta Analyses

Purpose To compare the effect of breast cancer radiotherapy as estimated from observational data with findings from randomized trials. Materials and Methods Rate ratios were obtained for selected end points among 13,932 women randomly assigned to receive radiotherapy or not in trials contributing to recent meta-analyses by the Early Breast Cancer Trialists’ Collaborative Group. Estimates of the same quantities were derived for 393,840 women registered with breast cancer in the US SEER registries between 1973 and 2008. Results In the randomized trials, radiotherapy after breast-conserving surgery reduced mortality from both breast cancer (rate ratio, 0.82; 95% CI, 0.75 to 0.90) and all causes (rate ratio, 0.92; 95% CI, 0.86 to 0.99). Reductions of similar magnitude were seen in the trials of radiotherapy after mastectomy in node-positive disease (rate ratios, breast cancer 0.84; 95% CI, 0.76 to 0.94; all causes, 0.89; 95% CI, 0.81 to 0.97). In the observational data, radiotherapy after breast-conserving surgery was associated with much larger mortality reductions (rate ratios, breast cancer, 0.64; 95% CI, 0.62 to 0.66; all causes, 0.63; 95% CI, 0.62 to 0.65), whereas radiotherapy after mastectomy in node-positive disease was associated with substantial increases in mortality (rate ratios, breast cancer, 1.34; 95% CI, 1.31 to 1.37; all causes, 1.23; 95% CI, 1.22 to 1.25). Detailed adjustment of the observational data for potential confounders did not reduce the divergence from the randomized data. Conclusion This study of mortality after radiotherapy for breast cancer found strikingly divergent results between the Early Breast Cancer Trialists’ Collaborative Group meta-analyses of randomized data and the SEER observational data, even when efforts had been made to remove confounding and selection biases. Nonrandomized comparisons are liable to provide misleading estimates of treatment effects. Therefore, they need careful justification every time they are used.

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