High-dose chemotherapy for patients with stage III breast cancer with homologous recombination deficiency: a discrete choice experiment among healthcare providers.

BACKGROUND AND PURPOSE: High-dose chemotherapy with autologous stem cell rescue (HDCT) is currently under investigation as a potential therapy for patients with stage III HER2-negative breast cancer with homologous recombination deficiency (HRD). In addition to survival, the impact on short- and long-term side effects might influence the uptake of HDCT by healthcare professionals. As part of the SUBITO trial, we investigated healthcare professionals' treatment (outcome) preferences for patients with HRD stage III HER2-negative breast cancer and established how healthcare professionals make trade-offs between these treatment outcomes. PATIENTS/MATERIAL AND METHODS: We conducted a discrete choice experiment in which healthcare professionals were asked to choose repeatedly between scenarios with two treatment options (HDCT or standard of care (SOC)) that varied in outcome with respect to 10-year overall survival (OS), short-term toxicity, long-term cognitive impairment, and premature menopause. We analysed treatment preferences, relative importance, and trade-offs using a multinomial logistic model. RESULTS AND INTERPRETATION: Thirty-five of the 151 dedicated breast cancer professionals with extensive experience in treating breast cancer patients completed the survey. The 10-year OS and long-term cognitive impairment were the most important attributes. The results indicate a requirement of 10.4% and 25.1% absolute additional improvement in the 10-year survival rate to justify accepting moderate or severe long-term cognitive impairment as a trade-off, respectively. Therefore, we found in our dataset that healthcare professionals expected a large improvement in 10-year OS to accept moderate to severe cognitive impairment. This information calls for further research into chemotherapy-related cognitive impairment, shared decision-making, and treatment preferences for patients with stage III breast cancer.

Early Cost-Effectiveness Analysis of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer Patients with Limited Peritoneal Carcinomatosis.

BACKGROUND: Gastric cancer patients with peritoneal carcinomatosis (PC) have a poor prognosis, with a median overall survival of 10 months when treated with systemic chemotherapy only. Cohort studies showed that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) might improve the prognosis for gastric cancer patients with limited PC. Besides generating trial data on clinical effectiveness, it is crucial to timely collect information on economic aspects to guide the reimbursement decision-making process. No previous data have been published on the cost(-effectiveness) of CRS/HIPEC in this group of patients. Therefore, we performed an early model-based cost-effectiveness analysis of CRS/HIPEC for gastric cancer patients with limited PC in the Dutch setting. METHODS: We constructed a two-state (alive-dead) Markov transition model to evaluate costs and clinical outcomes from a Dutch healthcare perspective. Clinical outcomes, transition probabilities and utilities were derived from literature and verified by clinical experts in the field. Costs were measured using two available representative cohorts (2010-2017): one 'systemic chemotherapy only' cohort and one 'CRS/HIPEC' cohort (n = 10 each). Incremental cost-utility ratios (ICURs) were expressed as Euros per quality-adjusted life-year (QALY). We performed probabilistic and deterministic sensitivity, scenario, and value-of-information analyses using a willingness-to-pay (WTP) threshold of €80,000/QALY, which reflects the Dutch norm for severe diseases. RESULTS: In the base-case analysis, CRS/HIPEC yielded more QALYs (increment of 0.68) and more costs (increment of €34,706) compared with systemic chemotherapy only, resulting in an ICUR of €50,990/QALY. The probability that CRS/HIPEC was cost effective compared with systemic chemotherapy alone was 64%. To reduce uncertainty, the expected value of perfect information amounted to €4,021,468. The scenario analyses did not alter the results and showed that treatment costs, lifetime health-related quality of life and overall survival had the largest influence on the model. CONCLUSIONS: The presented early cost-effectiveness analysis suggests that adding CRS/HIPEC to systemic chemotherapy for gastric cancer patients with limited PC has a good chance of being cost-effectiveness compared with systemic chemotherapy alone when using a WTP of €80,000/QALY. However, there is substantial uncertainty in view of the current available data on effectiveness. Results from the ongoing phase III PERISCOPE II trial are therefore crucial for further decisions on treatment policy and its cost-effectiveness.

High-dose chemotherapy with stem cell rescue to treat stage III homologous deficient breast cancer: factors influencing clinical implementation.

BACKGROUND: High-dose chemotherapy with autologous stem cell rescue (HDCT) is a promising treatment for patients with stage III, HER2-negative, homologous recombination deficient (HRD) breast cancer. Clinical effectiveness and cost-effectiveness are currently under investigation in an international multicenter randomized controlled trial. To increase the chance of successful introduction of HDCT into daily clinical practice, we aimed to identify relevant factors for smooth implementation using an early comprehensive assessment framework. METHODS: This is a qualitative, multi-stakeholder, exploratory research using semi-structured interviews guided by the Constructive Technology Assessment model, which evaluates the quality of a novel health technology by clinical, economic, patient-related, and organizational factors. Stakeholders were recruited by purposeful stratified sampling and interviewed until sufficient content saturation was reached. Two researchers independently created themes, categories, and subcategories by following inductive coding steps, these were verified by a third researcher. RESULTS: We interviewed 28 stakeholders between June 2019 and April 2021. In total, five overarching themes and seventeen categories were identified. Important findings for optimal implementation included the structural identification and referral of all eligible patients, early integration of supportive care, multidisciplinary collaboration between- and within hospitals, (de)centralization of treatment aspects, the provision of information for patients and healthcare professionals, and compliance to new regulation for the BRCA1-like test. CONCLUSIONS: In anticipation of a positive reimbursement decision, we recommend to take the highlighted implementation factors into consideration. This might expedite and guide high-quality equitable access to HDCT for patients with stage III, HER2-negative, HRD breast cancer in the Netherlands.

Cost-utility, cost-effectiveness, and budget impact of Internet-based cognitive behavioral therapy for breast cancer survivors with treatment-induced menopausal symptoms.

PURPOSE: Internet-based cognitive behavioral therapy (iCBT), with and without therapist support, is effective in reducing treatment-induced menopausal symptoms and perceived impact of hot flushes and night sweats (HF/NS) in breast cancer survivors. The aim of the current study was to evaluate the cost-utility, cost-effectiveness, and budget impact of both iCBT formats compared to a waiting list control group from the Dutch healthcare perspective. METHODS: A Markov model was constructed with a 5-year time horizon. Costs and health outcomes were measured alongside a randomized controlled clinical trial and included quality-adjusted life years (QALYs), overall levels of menopausal symptoms, and perceived impact of HF/NS. Uncertainty was examined using probabilistic and deterministic sensitivity analyses, together with a scenario analysis incorporating a different perspective. RESULTS: iCBT was slightly more expensive than the waiting list control, but also more effective, resulting in incremental cost-utility ratios of €23,331/QALY and €11,277/QALY for the guided and self-managed formats, respectively. A significant reduction in overall levels of menopausal symptoms or perceived impact of HF/NS resulted in incremental costs between €1460 and €1525 for the guided and €500-€753 for the self-managed format. The estimated annual budget impact for the Netherlands was €192,990 for the guided and €74,592 for the self-managed format. CONCLUSION: Based on the current trial data, the results indicate that both guided and self-managed iCBT are cost-effective with a willingness-to-pay threshold of well below €30,000/QALY. Additionally, self-managed iCBT is the most cost-effective strategy and has a lower impact on healthcare budgets.