A Randomized Trial of Trastuzumab Deruxtecan and Biology-Driven Selection of Neoadjuvant Treatment for HER2-positive Breast Cancer: ARIADNE

Non-metastatic HER2-positive Breast Cancer

Locally assessed rate of pCR at the molecularly HER2-enriched population, defined as ypT0/Tis, ypN0, as determined at the surgical specimen by a pathologist blinded to treatment assignment (intention-to-treat analysis).

Locally assessed rate of pCR, defined as ypT0/Tis, ypN0, at the two patient groups of the initial randomization of TCHP versus T-DXd, regardless of administered therapy after cycle 3, Locally assessed rate of pCR at ER-positive and luminal subgroup, Locally assessed rate of pCR at ER-negative and luminal subgroup, at the basal-like subgroup and the normal-like subgroup, Locally assessed rate of pCR at all molecular subgroups in the evaluable population, Rates of radiologic complete response after three courses of either standard therapy or T-DXd, Overall survival (OS), defined as time from randomization to death by any cause, for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd, Distant relapse-free survival (DRFS), defined as time from randomization to distant metastases or death by any cause, for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd, Event-free survival (EFS), defined as time from randomization to disease progression, breast cancer relapse, contralateral breast cancer, other malignant neoplasms, or death by any cause, for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd, Rates of complete radiologic response, for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd, Pathologic response according to Residual Cancer Burden Class, as described in 1, 2, for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd, Rate of breast conserving surgery, for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd, Rate of de-escalation of breast surgery (conversion from mastectomy to breast conserving surgery or de-escalation of complexity from an oncoplastic breast-conserving procedure to simple wide local excisions) for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd, Rate of Sentinel Lymph Node Dissection (SLND), for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd, Rate of de-escalation of axillary surgery (conversion from axillary lymph node dissection to either targeted axillary dissection or sentinel lymph node dissection) for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd., Rate of Sentinel Lymph Node detection, Targeted Axillary Dissection success and false-negative rates of these procedures in initially node-positive patients for each molecular group, including the comparison of TCHP versus T-DXd in HER2-enriched patients, and at the two patient groups of the initial randomization of TCHP versus T-DXd, Frequency and grade of adverse events (AE) (according to NCI CTCAE v. 5.0, see https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf) and rate of discontinuation due to toxicity, PRO endpoints including health related quality of life scores [European Organization for Research and Treatment of Cancer Quality of Life Instrument (EORTC QLQ-C30); European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ-BR23)]., Exploratory analyses of clinicopathologic characteristics as predictors for response, Discovery of biomarkers of response/resistance to administered neoadjuvant therapy at the protein, RNA and DNA levels in both tumor tissue and blood/plasma, as described in detail in protocol section 9.

Belgium, Norway, Sweden