Assessing the fiscal consequences of novel and existing treatments for triple negative breast cancer in Switzerland by applying a government perspective framework.

BACKGROUND: Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer that can impact patients' employment and workforce participation. This study estimates how the employment effects of TNBC impact government tax revenue and public benefits expenditure in Switzerland, representing the fiscal burden of disease (FBoD), and likely consequences of introducing new treatment options. METHODS: A four-state cohort model was used to calculate fiscal effects for two treatments: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab monotherapy (P + C→P) and neoadjuvant chemotherapy alone (C). Lifetime present values of tax revenue, social benefit payments, and healthcare costs were calculated for the average population and those undergoing treatment to assess the FBoD. RESULTS: An average TNBC patient treated with C and P + C→P is expected to generate CHF128,999 and CHF97,008 less tax than the average population, respectively, and require increased social benefit payments. Compared to C, 75% of the incremental healthcare costs of P + C→P are estimated to be offset through tax revenue gains. CONCLUSIONS: This analysis demonstrates that 75% of the additional costs of a new TNBC treatment option can be offset by gains in tax revenue. Fiscal analysis can be a useful tool to complement existing methods for evaluating new treatments.

Survival, treatment regimens and medical costs of women newly diagnosed with metastatic triple-negative breast cancer.

Individuals diagnosed with metastatic triple-negative breast cancer (mTNBC) suffer worse survival rates than their metastatic non-TNBC counterparts. There is little information on survival, treatment patterns, and medical costs of mTNBC patients in Asia. Therefore, this study aimed to examine 5-year survival, regimens of first-line systemic therapy, and healthcare costs of mTNBC patients in Taiwan. Adult females newly diagnosed with TNBC and non-TNBC as well as their survival data, treatment regimens and costs of health services were identified and retrieved from the Cancer Registry database, Death Registry database, and National Health Insurance (NHI) claims database. A total of 9691 (19.27%) women were identified as TNBC among overall BC. The 5-year overall survival rate of TNBC and non-TNBC was 81.28% and 86.50%, respectively, and that of mTNBC and metastatic non-TNBC was 10.81% and 33.46%, respectively. The majority of mTNBC patients received combination therapy as their first-line treatment (78.14%). The 5-year total cost in patients with metastatic non-TNBC and with mTNBC was NTD1,808,693 and NTD803,445, respectively. Higher CCI scores were associated with an increased risk of death and lower probability of receiving combination chemotherapy. Older age was associated with lower 5-year medical costs. In sum, mTNBC patients suffered from poorer survival and incurred lower medical costs than their metastatic non-TNBC counterparts. Future research will be needed when there are more treatment options available for mTNBC patients.

Systemic therapy, survival and end-of-life costs for metastatic triple-negative breast cancer: retrospective SEER-Medicare study of women age ≥65 years.

Aim: To analyze therapy for metastatic triple-negative breast cancer (mTNBC), factors contributing to survival and costs. Patients & methods: Using 2010-2016 SEER-Medicare data, we identified women (≥65 years) with mTNBC. Results: Of 302 eligible patients, 152 (50%) received systemic therapy. In multivariable regression analyses, only age <75 years was associated with therapy receipt (odds ratio: 2.91; 95% CI: 1.79-4.74); and only systemic therapy significantly reduced risk of death (hazard ratio: 0.34; 95% CI: 0.26-0.44). Median overall survival was 13.4 (95% CI: 11.3-15.1) vs 3.3 months (95% CI: 2.7-3.9) in therapy vs no-therapy cohorts. Mean per-patient-per-month costs <30 days before end-of-life/follow-up were $14,100 and $15,600 (2019 USD), respectively. Conclusion: Poor outcomes and high costs indicate need for more effective mTNBC therapy.

Early triple-negative breast cancer in women aged ≥65: retrospective study of outcomes, resource use and costs, 2010-2016.

Aim: To examine real-world treatment patterns and outcomes in neoadjuvant and adjuvant settings for early-stage triple-negative breast cancer (TNBC). Patients & methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients (≥65 years) with newly diagnosed stage II/III TNBC in 2010-2015 who had surgery plus neoadjuvant and/or adjuvant (systemic and/or radiation) therapy. Treatment, survival, healthcare resource use and costs were assessed through 2016. Results: Of 1569 patients (>99% women), 6%/74%/20% received neoadjuvant-only/adjuvant-only/both (neo + adj) therapies, respectively. Median overall survival was 23 months/not reached (NR)/78 months, with longer survival at stage II (NR/NR/78 months) than stage III (22/43/38 months). Mean per patient per month costs were $10,620 and $17,872 in neoadjuvant and adjuvant periods. Conclusion: These findings provide insights into clinical and economic outcomes for early-stage TNBC in 2010-2016.

Cost-effectiveness analysis of atezolizumab plus nab-paclitaxel for untreated metastatic triple-negative breast cancer.

Aim: To evaluate the cost-effectiveness of atezolizumab plus nab-paclitaxel (ANP) in the first-line treatment of metastatic triple-negative breast cancer (TNBC). Materials & methods: We developed a Markov model to evaluate the cost and effectiveness of ANP versus nab-paclitaxel in the first-line treatment of metastatic TNBC. Lifetime costs, life-years (LYs) and quality-adjusted LYs (QALYs) were estimated. Results: ANP provided an additional 0.16 QALYs (0.24 LYs) compared with nab-paclitaxel in intention-to-treat population. The corresponding incremental cost-effectiveness ratio was $786,131 per QALY gained. However, the incremental cost-effectiveness ratio decreased to $361,218 per QALY gained in the PD-L1 positive subgroup analysis. Conclusion: From the perspective of a US-payer, ANP is estimated not to be cost-effective in the first-line treatment of metastatic TNBC.

Cost-effectiveness analysis of atezolizumab in advanced triple-negative breast cancer.

BACKGROUND: The IMpassion130 trial demonstrated that adding atezolizumab to nanoparticle albumin-bound (nab)-paclitaxel improved the survival of patients with untreated, advanced, programmed death ligand 1 (PDL1)-positive triple-negative breast cancer (TNBC). In view of the high cost of immunotherapy, it is important to examine its value with respect to both benefits and costs. In this study, the cost-effectiveness of atezolizumab/nab-paclitaxel combination therapy relative to nab-paclitaxel monotherapy was evaluated for the first-line treatment of advanced, PDL1-positive TNBC, from a healthcare system perspective. METHODS: A three-state partitioned-survival model was developed to compare the clinical and economic outcomes of treatment with atezolizumab/nab-paclitaxel combination therapy with nab-paclitaxel monotherapy in patients with advanced TNBC. Clinical data were obtained from the IMpassion130 trial and extrapolated to 5 years. Health state utilities were retrieved from the literature, while direct costs (in Singapore dollars, S$) were sourced from public healthcare institutions in Singapore. The primary outcomes of the model were life years (LYs), quality-adjusted LYs (QALYs), costs and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of specific assumptions and uncertainties. RESULTS: Adding atezolizumab to nab-paclitaxel resulted in an additional 0.361 QALYs (0.636 LYs) at an ICER of S$324,550 per QALY gained. The ICER remained high at S$67,092 per QALY even when atezolizumab was priced zero. One-way sensitivity analysis showed that the ICER was most sensitive to variations in the cost of atezolizumab and the time horizon. Scenario analyses confirmed that the ICERs remained high even under extremely favourable assumptions. CONCLUSIONS: Given the exceedingly high ICER, adding atezolizumab to nab-paclitaxel was unlikely to represent good value for money for the treatment of advanced PDL1-positive TNBC. Our findings will be useful in informing funding policy decisions alongside other considerations such as comparative effectiveness, unmet need and budget impact.

The economic burden of metastatic breast cancer in Spain.

Objectives: The study aimed to estimate the burden of metastatic breast cancer (mBC) in Spain over 5 years. Methods: An incidence-based cost-of-illness model was developed in which a cohort of patients with mBC was followed from the diagnosis of metastatic disease over 5 years or death. Resource use data were collected through a physician survey conducted with 10 clinical experts in Spain. The model distinguished patients according to HER2 and hormonal receptor (HR) status, and followed the patient cohort in monthly cycles. Results: The incident cohort was estimated to be 2,923 patients with mBC, consisting of 1,575 HER2-/HR+, 520 HER2+/HR+, 324 HER2+/HR-, and 503 triple negative patients. The estimated mean survival over the 5-year time period was 2.51 years, on average, with longer survival of 3.36 years for HER2+/HR+, 2.41 years for HER2-/HR+, 2.82 years for HER2+/HR- and shortest mean survival of 1.74 years for triple negative patients. The total costs were €469,92,731 for the overall population, €190,079,787 for the HER2-/HR+, €151,045,260 for the HER2+/HR+, €80,827,171 for the HER2+/HR- and €47,540,512 for the triple negative subgroups over 5 years. Per patient total costs were €160,642 on average, €120,664 for HER2-/HR+, €290,346 for HER2+/HR+, €249,152 for HER2+/HR-and €94,572 for triple negative patients over 5 years. Conclusions: The economic burden of mBC in Spain is significant, but differs by HER2 and HR status. HER2-/HR +patients account for the highest burden due to the prevalence of this category, but HER2+/HR +patients have the highest per patient costs.

Advocacy for a New Oncology Research Paradigm: The Model of Bevacizumab in Triple-Negative Breast Cancer in a French Cohort Study.

BACKGROUND: Triple-negative breast cancer remains a disease with poor prognosis and few treatment options, due to the lack of therapeutic targets. Bevacizumab, the first anti-VEGF agent approved in the treatment of cancer, has demonstrated efficacy in breast cancer in combination with paclitaxel for the first-line treatment of HER2-negative metastatic breast cancer. Despite the fact that the benefit was particularly significant for triple-negative breast cancer with its approval in 2008 by the FDA, this decision was later reversed as there was no improvement in overall survival in addition to significant costs. OBJECTIVES: The scope of the present study is to focus on the role of bevacizumab in triple-negative breast cancer through the analysis of overall survival, progression-free survival, and cost benefit among 45 patients in a French monocentric study and to discuss new paradigms of endpoints. METHODS: All patients diagnosed with metastatic triple-negative breast cancer, for whom first-line treatment was bevacizumab in combination with paclitaxel between January 2011 and April 2018 were included in this single-center retrospective study, and a chart review of all recruited subjects was performed from medical records. RESULTS: In this real-life study among 45 patients with metastatic triple-negative breast cancer, bevacizumab provided a significant benefit for a category of patients, with longer median progression-free survival and the ability of maintenance therapy associated to limited side effects. CONCLUSIONS: Beyond being the phoenix of breast oncology and a magnet of controversy, the case of bevacizumab in metastatic breast cancer highlights one of the greatest challenges in oncology, namely to balance modest clinical benefits with exponential costs. A balance needs to be found between health care affordability, high price of progress, and the best medical decision for the patients, in order to avoid the "unbreathable tipping point" we are actually dealing with.

Overall survival, costs and healthcare resource use by number of regimens received in elderly patients with newly diagnosed metastatic triple-negative breast cancer.

AIM: This analysis estimated the overall survival, treatment patterns and economic burden of elderly metastatic triple-negative breast cancer patients. MATERIALS & METHODS: Patients (≥66 years) with metastatic triple-negative breast cancer were identified from the SEER-Medicare database. Treatment patterns were defined in terms of first, second and third or more regimens. Healthcare resource use and costs were reported over the follow-up period and over the treatment duration of each regimen. RESULTS:  A total of 51% of patients did not receive chemotherapy. Taxanes were most commonly used. Median survival was 7 months. The mean cumulative (per patient per month) cost per patient was US$73,586 (US$10,084). Mean cost in first and second regimen were US$26,950 and US$33,347. CONCLUSION: About half of patients did not receive chemotherapy. Receipt of increasing regimens led to higher mean costs and healthcare resource use.

Signaling pathway inhibitors target breast cancer stem cells in triple-negative breast cancer.

The present study aimed to investigate the efficacy of five signaling pathway inhibitors, N-[N-(3,5­difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, vismodegib, salinomycin, ruxolitinib and stattic, as novel therapeutic agents that target breast cancer stem cells (BCSCs) in triple-negative breast cancer (TNBC). The in vitro anti-proliferative, anti-invasive, pro-apoptotic and inhibitory effects on BCSC self-renewal of these signaling pathway inhibitors on the TNBC stem cell line HCC38 were examined by MTT assays, Matrigel invasion assays, flow cytometry and suspension mammosphere assays, respectively. For the in vivo study, another TNBC stem cell line, HCC1806, pretreated with these signaling pathway inhibitors, was inoculated into female nonobese diabetic/severe combined immunodeficient mice, and the tumor volumes were measured following tumor formation. Treatment of HCC38 cells with each signaling pathway inhibitor significantly decreased TNBC cell proliferation, cell invasion and mammosphere formation while inducing cell apoptosis by inhibiting the protein expression or phosphorylation of downstream signaling molecules. In the xenograft mouse models, tumor formation and growth of HCC1806 cells pretreated with each signaling pathway inhibitor were effectively suppressed. Treatment with these signaling pathway inhibitors may provide a novel therapeutic strategy against TNBC by targeting BCSCs, thus providing promising insight for clinical applications in patients with TNBC.

Clinical and economic burden associated with stage III to IV triple-negative breast cancer: A SEER-Medicare historical cohort study in elderly women in the United States.

BACKGROUND: The current study was performed to describe patient characteristics, treatment patterns, survival, health care resource use (HRU), and costs among older women in the United States with advanced (American Joint Committee on Cancer stage III/IV) triple-negative breast cancer (TNBC) in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. METHODS: Women who were aged ≥66 years at the time of diagnosis and diagnosed with advanced TNBC between January 1, 2007, and January 1, 2011, in the SEER-Medicare database and who were followed for survival through December 31, 2013, were eligible. Patient demographic and clinical characteristics at the time of diagnosis, subsequent treatment patterns, and survival outcomes were analyzed. HRU and costs for the first 3 months after diagnosis, the last 3 months of life, and the time in between are summarized. All analyses were stratified by American Joint Committee on Cancer stage of disease. RESULTS: There were 1244 patients newly diagnosed with advanced TNBC; the majority were aged ≥75 years (61% with stage III disease and 57.4% with stage IV disease) and white (>70% of patients in both disease stage groups). The most common treatment approaches were surgery combined with chemotherapy for patients for stage III disease (50.6%) and chemotherapy alone or with radiotherapy for patients with stage IV disease (31.3%). Diverse chemotherapy regimens were administered for each line of therapy; nevertheless, the medications used were consistent with national guidelines. Patients with stage III and stage IV disease were found to have a similar mean number of hospitalizations and outpatient visits, but mean monthly costs were greater for patients with stage IV disease at all 3 time points. The mean cost per patient-month (in 2013 US dollars) was $4810 for patients with stage III disease and $9159 for patients with stage IV disease. CONCLUSIONS: Among older women with advanced TNBC, significant treatment variations and considerable HRU and costs exist. Further research is needed to find effective treatments with which to reduce the clinical and economic burden of this disease. Cancer 2018;124:2104-14. © 2018 American Cancer Society.

Outcomes research examining treatments, quality of life and costs in HER2-negative and triple-negative metastatic breast cancer: a systematic literature review.

AIM: With the aggregation of real-world data in healthcare, opportunities for outcomes research are growing. In this study, we summarize published literature examining comparative effectiveness research (CER), treatment patterns, quality of life (QoL) and costs in HER2-negative and triple-negative (TN) metastatic breast cancer (mBC). METHODS: PubMed (2010-January 2016) and four conferences (2013-January 2016) were searched using MeSH/keywords, including mBC, QoL, morbidity and therapeutics. Studies relating to CER, treatment patterns, QoL, costs or treatment appropriateness in US patients with HER2-negative/TN mBC were included in the review. RESULTS: Of 1782 identified records, 33 studies met full inclusion criteria: seven related to CER, 18 to treatment patterns, one to treatment appropriateness/navigation, two to QoL and five to costs. Studies varied in objectives, designs and outcomes. Study designs included retrospective chart reviews (52%), retrospective secondary database analyses (27%), economic models (12%), physician surveys (6%) and patient surveys (3%). 25 studies reported results on HER2-negative mBC, six on TN mBC and two on both subtypes. The most common end points examined were treatment patterns, overall survival and progression-free survival. CONCLUSION: Outcomes research in HER2-negative mBC in the USA was limited, specifically among TN patients, indicating an opportunity for further research in this high unmet need population. Endpoints and treatment options varied, thus, it is difficult to draw summary conclusions about these studies. Outcomes research examining real-world data in mBC has increased in recent years, and may continue to grow with the implementation of new policy programs.

Cavity Shaving Reduces Involved Margins and Reinterventions Without Increasing Costs in Breast-Conserving Surgery: A Propensity Score-Matched Study.

BACKGROUND: Currently, reinterventions for involved margins after breast-conserving surgery remain common. The aim of this study was to assess the capability of the cavity shave margins (CSM) technique to reduce positive margin rates and reoperations compared with simple lumpectomy (SL). The impact of CSM on the various biological portraits of breast cancer and costs were also investigated. METHODS: A retrospective review of 976 consecutive patients from a single center was performed; 164 patients underwent SL and 812 received CSM. All patients were treated with an oncoplastic approach. and involved margins and reoperations were compared for each group. To avoid selection bias, propensity score-matched analysis was performed before applying a logistic regression model. Main outcomes were reanalyzed for each biological portrait, and surgery and hospitalization costs for SL and CSM were compared. RESULTS: Clear margins were found in 98.3% of patients in the CSM group versus 74.4% of patients in the SL group (p < 0.001). The reoperation rate was 18.9% in the SL group and 1.9% in the CSM group (p < 0.001). After propensity score-matched logistic regression, odds ratio (OR) for positive final margin status was 6.2 (95% confidence interval [CI] 2.85-13.46; p < 0.001) without CSM, while OR for reintervention was 5.46 (95% CI 2.21-13.46; p < 0.001). CSM significantly reduced positive margins and reexcisions for Luminal A, Luminal B, and triple-negative breast cancers (p < 0.001, p < 0.001, and p = 0.0137, respectively). SL had higher global costs compared with CSM: €193,630.6 versus €177,830 for 100 treated patients (p = 0.009). CONCLUSIONS: CSM reduces reexcisions, mainly in luminal breast cancers, without increasing costs.

Decisions on Further Research for Predictive Biomarkers of High-Dose Alkylating Chemotherapy in Triple-Negative Breast Cancer: A Value of Information Analysis.

OBJECTIVES: To inform decisions about the design and priority of further studies of emerging predictive biomarkers of high-dose alkylating chemotherapy (HDAC) in triple-negative breast cancer (TNBC) using value-of-information analysis. METHODS: A state transition model compared treating women with TNBC with current clinical practice and four biomarker strategies to personalize HDAC: 1) BRCA1-like profile by array comparative genomic hybridization (aCGH) testing; 2) BRCA1-like profile by multiplex ligation-dependent probe amplification (MLPA) testing; 3) strategy 1 followed by X-inactive specific transcript gene (XIST) and tumor suppressor p53 binding protein (53BP1) testing; and 4) strategy 2 followed by XIST and 53BP1 testing, from a Dutch societal perspective and a 20-year time horizon. Input data came from literature and expert opinions. We assessed the expected value of partial perfect information, the expected value of sample information, and the expected net benefit of sampling for potential ancillary studies of an ongoing randomized controlled trial (RCT; NCT01057069). RESULTS: The expected value of partial perfect information indicated that further research should be prioritized to the parameter group including "biomarkers' prevalence, positive predictive value (PPV), and treatment response rates (TRRs) in biomarker-negative patients and patients with TNBC" (€639 million), followed by utilities (€48 million), costs (€40 million), and transition probabilities (TPs) (€30 million). By setting up four ancillary studies to the ongoing RCT, data on 1) TP and MLPA prevalence, PPV, and TRR; 2) aCGH and aCGH/MLPA plus XIST and 53BP1 prevalence, PPV, and TRR; 3) utilities; and 4) costs could be simultaneously collected (optimal size = 3000). CONCLUSIONS: Further research on predictive biomarkers for HDAC should focus on gathering data on TPs, prevalence, PPV, TRRs, utilities, and costs from the four ancillary studies to the ongoing RCT.

Patterns of resource utilization and cost for postmenopausal women with hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer in Europe.

BACKGROUND: Healthcare resource utilization in breast cancer varies by disease characteristics and treatment choices. However, lack of clarity in guidelines can result in varied interpretation and heterogeneous treatment management and costs. In Europe, the extent of this variability is unclear. Therefore, evaluation of chemotherapy use and costs versus hormone therapy across Europe is needed. METHODS: This retrospective chart review (N = 355) examined primarily direct costs for chemotherapy versus hormone therapy in postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer across 5 European countries (France, Germany, The Netherlands, Belgium, and Sweden). RESULTS: Total direct costs across the first 3 treatment lines were approximately €10,000 to €14,000 lower for an additional line of hormone therapy-based treatment versus switching to chemotherapy-based treatment. Direct cost difference between chemotherapy-based and hormone therapy-based regimens was approximately €1900 to €2500 per month. Chemotherapy-based regimens were associated with increased resource utilization (managing side effects; concomitant targeted therapy use; and increased frequencies of hospitalizations, provider visits, and monitoring tests). The proportion of patients taking sick leave doubled after switching from hormone therapy to chemotherapy. CONCLUSIONS: These results suggest chemotherapy is associated with increased direct costs and potentially with increased indirect costs (lower productivity of working patients) versus hormone therapy in HR+, HER2- advanced breast cancer.

Early stage cost-effectiveness analysis of a BRCA1-like test to detect triple negative breast cancers responsive to high dose alkylating chemotherapy.

PURPOSE: Triple negative breast cancers (TNBC) with a BRCA1-like profile may benefit from high dose alkylating chemotherapy (HDAC). This study examines whether BRCA1-like testing to target effective HDAC in TNBC patients can be more cost-effective than treating all patients with standard chemotherapy. Additionally, we estimated the minimum required prevalence of BRCA1-like and the required positive predictive value (PPV) for a BRCA1-like test to become cost-effective. METHODS: Our Markov model compared 1) the incremental costs; 2) the incremental number of respondents; 3) the incremental number of Quality Adjusted Life Years (QALYs); and 4) the incremental cost-effectiveness ratio (ICER) of treating TNBC women with personalized HDAC based on BRCA1-like testing vs. standard chemotherapy, from a Dutch societal perspective and a 20-year time horizon, using probabilistic sensitivity analysis. Furthermore, we performed one-way sensitivity analysis (SA) to all model parameters, and two-way SA to prevalence and PPV. Data were obtained from a current trial (NCT01057069), published literature and expert opinions. RESULTS: BRCA1-like testing to target effective HDAC would presently not be cost-effective at a willingness-to-pay threshold of €80.000/QALY (€81.981/QALY). SAs show that PPV drives the ICER changes. Lower bounds for the prevalence and the PPV were found to be 58.5% and 73.0% respectively. CONCLUSION: BRCA1-like testing to target effective HDAC treatment in TNBC patients is currently not cost-effective at a willingness-to-pay of €80.000/QALY, but it can be when a minimum PPV of 73% is obtained in clinical practice. This information can help test developers and clinicians in decisions on further research and development of BRCA1-like tests.