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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Antitumor treatment plan

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Ziwen Zhang; Phone Number: +86 13588318799; Email: 16660496@qq.com

Study Locations

• China
  • Hangzhou
    • Zhejiang, Hangzhou, China, 310000
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Ziwen Zhang; Phone Number: +86 13588318799; Email: 16660496@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with HER-2 positive advanced or metastatic breast cancer.

Description

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.

   -

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
B; The treatment plan was changed from HPy plus chemotherapy to HP plus chemotherapy.	Drug: Antitumor treatment plan; This research project included valid data from 600 patients with HER-2 positive advanced or metastatic breast cancer. They were randomly divided into Group A (transition from HP + chemotherapy to HPy + chemotherapy) or Group B (transition from HPy + chemotherapy to HP + chemotherapy) in a 1:1 ratio. Each group had approximately 300 patients. If the patients failed in their first-line treatment, they would switch to another treatment regimen in the second-line treatment. All patients were stopped from treatment when their condition progressed, toxicity became intolerable, or for other reasons. The treatment cycles were recorded.
A; The treatment plan was changed from HP plus chemotherapy to HPy plus chemotherapy.	Drug: Antitumor treatment plan; This research project included valid data from 600 patients with HER-2 positive advanced or metastatic breast cancer. They were randomly divided into Group A (transition from HP + chemotherapy to HPy + chemotherapy) or Group B (transition from HPy + chemotherapy to HP + chemotherapy) in a 1:1 ratio. Each group had approximately 300 patients. If the patients failed in their first-line treatment, they would switch to another treatment regimen in the second-line treatment. All patients were stopped from treatment when their condition progressed, toxicity became intolerable, or for other reasons. The treatment cycles were recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS by Investigator assessment per RECIST 1.1	The PFS of patients who had previously received trastuzumab treatment and then switched to another targeted therapy after progression following two targeted strategies after recurrence.	60 mouths

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	The OS of patients after conversion application of two targeted strategies in the treatment of post-progression cases.	60 mouths

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Investigators: Principal Investigator: Hai Hu, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: January 22, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: IIT-2025-109

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No