A Prospective, Randomized Controlled Phase II Trial Investigating the Optimal Timing of Antibody Drug Conjugates in Advanced HER2-Negative Breast Cancer Patients
Objective: To compare the difference in PFS2 (Time from randomization to disease progression after second therapy) between antibody-drug conjugate (ADC) followed by chemotherapy versus chemotherapy followed by ADC in the treatment of advanced HER2-negative breast cancer. Secondary
Objectives: To compare overall survival (OS), adverse events, patient-reported outcomes, and cost-effectiveness between the two treatment sequences. Additionally, to identify potential biomarkers predictive of benefit from frontline ADC therapy.
• Female patients aged 18-75 years;
• Histologically confirmed advanced HER2-negative breast cancer, including IHC 2+/ISH-, IHC 1+/ISH-, and IHC 0/ISH- subtypes;
• Completed first-line combination chemotherapy for advanced/metastatic disease (specific regimen not restricted), with disease progression (PD) evaluated per RECIST criteria (HR-positive patients must have received at least one line of endocrine therapy);
• Electrocorticography (ECOG) performance status \< 2;
• Estimated life expectancy ≥ 12 weeks;
• Adequate bone marrow function, defined as:
‣ ANC ≥ 1.5 × 10⁹/L
⁃ Platelets ≥ 90 × 10⁹/L
⁃ Hemoglobin ≥ 90 g/L
• Adequate hepatic and renal function, defined as:
‣ Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
⁃ AST or ALT ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases)
⁃ Creatinine clearance ≥ 60 mL/min
• Signed informed consent obtained prior to any study-related procedures or treatments, confirming the patient's willingness to participate and comply with study requirements.