This study is looking at a new combination of two drugs-eribulin and anlotinib-for patients with HER2-negative advanced breast cancer. Participants in this study have already tried other treatments like T-DXd or SG, but their cancer has gotten worse, and there are currently no standard treatment options left for them. Researchers believe that using these two drugs together may work better than using either one alone based on how they target cancer cells. The goal is to offer a new choice and help improve survival for these patients.
Female patients aged ≥ 18 years with pathologically confirmed metastatic or locally advanced unresectable breast cancer.
HER2-negative status, defined as immunohistochemistry (IHC) 0 or 1+, or IHC 2+ with negative HER2 gene amplification by fluorescence in situ hybridization (FISH). If multiple specimens have been tested, the most recent test result will be used for determination.
Prior treatment with anthracycline- or taxane-containing chemotherapy, including in the neoadjuvant or adjuvant setting.
Intolerance or disease progression following prior treatment with an antibody-drug conjugate (ADC), without the initiation of a new treatment regimen after ADC therapy.
Untreated active brain metastases. Patients with asymptomatic central nervous system (CNS) metastases or those with stable brain metastases following radiotherapy are eligible.
Known spinal cord compression or active CNS metastases that have not been treated with surgery or radiotherapy, except for patients who have been stable for at least 1 month after treatment and have discontinued corticosteroids for > 2 weeks.
HER2-positive status, defined as immunohistochemistry (IHC) 3+, or IHC 2+ with positive HER2 gene amplification by fluorescence in situ hybridization (FISH). Patients with a prior HER2-positive status but who are HER2-negative per the most recent pathology test are eligible.
History of clinically significant cardiovascular, hepatic, respiratory, renal, hematological, endocrine, or neuropsychiatric diseases.
Single group
Eribulin in Combination with Anlotinib
DrugParticipants will receive eribulin mesylate administered as a 1-hour intravenous infusion at a dose of 1.4 mg/m² on Days 1 and 8 of each 21-day cycle. Anlotinib will be administered orally at a dose of 8 mg once daily on Days 1 through 14 of each 21-day cycle, followed by a 7-day rest period. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent.
Progression free survival
Progression free survival (PFS) is defined as the time from the first dose of study treatment to the first documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause, whichever occurs first. For patients who have not experienced disease progression or death at the time of analysis, PFS will be censored at the date of the last adequate tumor assessment. If no post-baseline tumor assessment is available, PFS will be censored at the date of first dose. Disease progression is determined by investigator assessment based on imaging evaluations (e.g., CT, MRI) performed at baseline and at scheduled time points throughout the study. Unit of Measure: Months
Overall survival
Overall survival (OS) is defined as the time from the first dose of study treatment to death from any cause. For patients who are alive at the time of analysis, OS will be censored at the last known date the patient was known to be alive. If no post-baseline follow-up information is available, OS will be censored at the date of first dose. Survival status is collected through scheduled follow-up visits and/or via telephone contact at the end of the study. Unit of Measure: Months
Safety
Safety and tolerability will be assessed by evaluating the incidence, severity, and causality of adverse events (AEs) and serious adverse events (SAEs). AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Unit of Measure: Number of participants
Quality of Life (QoL)
Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the breast cancer-specific module. Unit of Measure: Score on a scale
Prevalence of PIK3CA, ESR1, and GATA3 (PEG) Gene Mutations
The presence or absence of mutations in the PIK3CA, ESR1, and GATA3 genes (PEG gene panel) will be assessed using next-generation sequencing (NGS) performed on tumor tissue or circulating tumor DNA (ctDNA) collected at baseline. Unit of Measure: Mutant-type category (Mutant vs. Wild-type)
Change in Metabolite Concentrations
Blood samples will be collected at baseline and during study treatment. Metabolomic profiling will be performed using liquid chromatography-mass spectrometry (LC-MS) to identify and quantify the concentration of specific metabolites. Unit of Measure: Concentration (μM or relative abundance)
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