Résumé
Background: Triple-negative breast cancer (TNBC), accounts for 15% to 20% of all breast cancers. It is characterized by the absence of 3 receptors (estrogen/progesterone/human epidermal growth factor 2) which limits the treatment options. Currently a therapeutic sequence for patients with mTNBC is first-line chemotherapy with or without immunotherapy, followed by sacituzumab govitecan then by successive chemotherapy lines. Considering the toxicity of these treatments there is a need to identify and monitor the signs and symptoms (S&S) of adverse events (AE). Early identification of these S&S, with appropriate management may prevent severe and fatal AEs, reduce dose delays and treatment discontinuations, thus optimizing treatment and possibly improving survival outcomes. Cureety is a digital remote monitoring platform, specifically designed to facilitate the monitoring of S&S of treatment-specific AEs and disease progression in cancer patients. Cureety integrates the Cureety TechCare algorithm for patient clinical classification, a CE-marked medical device. We hypothesize that patients with mTNBC may benefit from Cureety during systemic treatments by improving the identification of S&S of potentially severe/ AEs at early stages or early progression symptoms. Trial design: ALTERNATIVE is a French, multicentre, randomized, phase III trial comparing standard of care (SoC) with or without telemonitoring. The telemonitoring will comprise weekly AE and S&S evaluations and their analyses by Cureety. The randomization will be stratified by planned first-line treatment (immunotherapy: yes vs no) and ECOG PS (0 vs 1-2). Eligibility criteria: Patients aged ≥18 years, with mTNBC, ECOG PS ≤2, initiating first-line systemic treatment. The patient must be able and willing to complete web-based self-report questionnaires. Specific aims: To assess the effectiveness of SoC with digital telemonitoring compared to SoC alone, in terms of Time to definitive Health-Related Quality-of-Life score Deterioration (TUDD), Hospitalization Free Survival (HFS) and OS. The secondary objectives will include contribution on patient’s safety, treatment compliance and extent of exposure, compliance with telemonitoring, patient and medical team satisfaction with telemonitoring, global patient satisfaction with care, and socio-economic data. Sample size: A two-sided sequential logrank test with an overall sample size of 472 subjects for 384 events achieves 90% power at a 5% two-sided significance level to detect a hazard ratio (HR) of 0.72 when the median TUDD is 4.3 months without telemonitoring and 6 months with telemonitoring. The planned study duration is 42 months (18 months of accrual and 24 months of follow up). An interim futility analysis is planned after 157 TUDD events using an alpha-spending function of O'Brien-Fleming Analog. Statistical methods: TUDD, defined as the time from randomization to the first deterioration of ≥ 10 points out of 100 in the global health status (GHS) score (items 29 and 30 of the QLQ-C30), will be analysed using the Kaplan-Meier method. The median and Q1, Q3 event times for each arm and the corresponding 2-sided 95% confidence intervals (CIs) will be provided. A two-sided log-rank test stratified for the randomization stratification factors will be used to compare TUDD between the two study groups. The Cox regression model, stratified for the same stratification factors, will be fitted, and the estimated HR and 2-sided 95% CIs will be provided. To preserve the alpha risk at 5% for the two analyses, the p-value will be 0.00325 at the first analysis and 0.0492 at the final analysis. To control the overall type I error at 5%, once the superiority with TUDD is established, and the study is conclusive, HFS then OS will also be tested at 5% significance level using a hierarchical order. If the study is not conclusive for TUDD these endpoints will still be analysed but will be interpreted as exploratory. Funding Bpifrance and Cureety Citation Format: Martin Babau, Florence Joly, Frederic Fiteni, Aurore Caumont-Prim, Trevor Stanbury, David Perol, Charles Parnot, Francois-Guirec Champoiseau, Adeline Poitou, Jerome Lemoonier, Francois Montestruc. randomized phase III study comparing the digital telemonitoring platform “CUREETY TECHCARE” to usual standard of care in patients with triple negative metastatic breast cancer initiating a first-line systemic treatment: ALTERNATIVE [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-08-25.