Switching between two HER2-targeted regimens (HP+chemotherapy vs HPy+chemotherapy) after progression in advanced HER2-positive 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 project tests whether switching between two HER2-targeted regimens (HP+chemo and HPy+chemo) after progression helps people with HER2-positive advanced or metastatic breast cancer.

Quick facts

• Study type: Observational
• Enrollment: 600 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: trastuzumab, pertuzumab, pyrotinib, chemotherapy
• Locations: 1 site (Zhejiang, Hangzhou)
• Trial ID: NCT07455188 on ClinicalTrials.gov

What this trial studies

This multicenter, natural-selection observational study plans to collect real-world data from about 600 patients with HER2-positive advanced or metastatic breast cancer across participating centers. Patients will be naturally allocated roughly 1:1 to either switch from HP + chemotherapy to HPy + chemotherapy or from HPy + chemotherapy to HP + chemotherapy, with treatment switching occurring at second-line after first-line failure. Predefined subgroups — including de novo stage IV patients, those with brain metastases, and patients without prior trastuzumab exposure — will be analyzed separately and not pooled into the overall analysis. Outcomes will include measures of efficacy and safety related to sequencing these targeted regimens in routine clinical practice.

Who should consider this trial

Good fit: Adult women (≥18 years) with histologically confirmed HER2-positive advanced or metastatic breast cancer, at least one measurable lesion per RECIST 1.1, ECOG 0–2, and whose treatment history fits the protocol-specified first-line/second-line sequencing are ideal candidates.

Not a fit: Patients with de novo stage IV disease, those with brain metastases, or those who relapsed within one year after prior trastuzumab/TKI may not be represented in the main comparison and may not receive clear benefit from the overall findings.

Why it matters

Potential benefit: If successful, the findings could help clinicians choose a better sequencing strategy that improves disease control and tolerability for patients with HER2-positive advanced breast cancer.

How similar studies have performed: Sequencing different HER2-targeted agents after progression has been explored before with mixed but sometimes positive results, though direct real-world comparisons of these exact regimens are limited.

Eligibility criteria

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.

Where this trial is running

Zhejiang, Hangzhou

• Zhejiang Cancer Hospital — Zhejiang, Hangzhou, China (Recruiting)

Study contacts

• Principal investigator: Hai Hu — Zhejiang Cancer Hospital
• Study coordinator: Ziwen Zhang

Conditions Breast Cancer