A Study on the Efficacy and Safety of Switching Between Two Targeted Strategies, HP+Chemotherapy and HPy+Chemotherapy, After Treatment Progression in HER-2 Positive Advanced or Metastatic Breast Cancer

A Study on the Efficacy and Safety of Switching Between Two Targeted Strategies, HP+Chemotherapy and HPy+Chemotherapy, After Treatment Progression in HER-2 Positive Advanced or Metastatic Breast Cancer

This study adopts a multicenter, natural selection, observational design, and plans to enroll patients with HER-2 positive advanced or metastatic breast cancer treated at approximately 20 research centers nationwide. Patients with de novo stage IV disease or those with recurrent metastatic breast cancer who have not previously received trastuzumab, as well as patients with brain metastases, will be included for separate stratified efficacy analysis and will not be included in the overall analysis. The study plans to enroll effective data from 600 HER-2 positive advanced or metastatic breast cancer patients, who will be naturally allocated in a 1:1 ratio to either Group A (switching from HP + chemotherapy to HPy + chemotherapy) or Group B (switching from HPy + chemotherapy to HP + chemotherapy), with each group comprising approximately 300 patients. If first-line treatment fails, patients will switch to the alternative regimen in second-line treatment. All patients will continue treatment until disease progression, intolerable toxicity, or other reasons lead to discontinuation, with the number of treatment cycles recorded. The study is divided into three phases: screening/baseline period, treatment period (treatment period 1 + treatment period 2), and survival follow-up period. If patients develop intolerance to taxanes during treatment, clinicians may select alternative chemotherapy regimens such as vinorelbine, capecitabine, or eribulin based on clinical judgment. During the treatment period, patients will be followed up every two cycles, during which clinical data will be collected, including disease status assessments, laboratory tests, study drug usage, concomitant medications, and adverse events. After chemotherapy completion or treatment discontinuation, subsequent maintenance therapy, such as continued dual-targeted maintenance, may be administered by clinicians based on clinical needs until disease progression or intolerable toxicity occurs. Survival follow-up will be conducted every three months (for up to three years), with patient survival status recorded.

Inclusion Criteria:

1. Voluntarily signed the informed consent form with good compliance.

2. Female, aged 18 years or older.

3. Histologically confirmed diagnosis of HER2-positive advanced or metastatic breast cancer.

4. Metastatic lesions confirmed by MRI/contrast-enhanced CT, with at least one measurable lesion according to RECIST 1.1 criteria.

5. For patients previously treated with trastuzumab or tyrosine kinase inhibitors (TKIs) in the early-stage setting, recurrence must have occurred more than 1 year after the completion of prior treatment.

6. ECOG performance status score of 0-2.

7. Eligible patients meeting the treatment criteria specified in this study protocol may be included. This includes:Patients whose prior first-line and second-line treatments both align with the requirements of this protocol；Patients currently receiving second-line treatment whose prior first-line treatment aligns with the requirements of this protocol；The above populations may have previously received or not received trastuzumab and/or pertuzumab, small-molecule tyrosine kinase inhibitors (e.g., pyrotinib, etc.), and may include patients with brain metastases, among others.

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Exclusion Criteria:

1. Known allergy to the drugs involved in this trial or their excipients.
2. Current or recent use of medications that may affect the metabolism or efficacy of pyrotinib or trastuzumab, such as strong CYP3A4 inhibitors (e.g., itraconazole, fluconazole, etc.), strong CYP3A4 inducers (e.g., rifampicin, efavirenz, etc.), or other drugs that may influence the plasma concentration of these two agents.
3. Pregnant or lactating women.
4. Major surgery within 4 weeks prior to the start of study drug administration, with incomplete recovery. Minor procedures such as tumor biopsy, thoracentesis, or venous catheter placement are permitted.
5. Presence of severe systemic diseases and/or uncontrolled infections.
6. Concurrent conditions considered by the investigator to pose a serious risk to patient safety or interfere with the patient's ability to complete the study (e.g., severe hypertension, diabetes, thyroid disorders, concurrent hepatitis B/C, or other active infections).
7. History of other malignancies.
8. Psychiatric illness, cognitive impairment, or inability to comply with the trial protocol and follow-up.
9. Other conditions deemed by the investigator to render the participant unsuitable for inclusion.