Real-world Study of Pyrotinib-containing Regimens of Advanced HER2-positive Breast Cancer

Real-world Study of Pyrotinib-containing Regimens in First-line or Second-line Treatment of Advanced HER2-positive Breast Cancer

Given that pyrotinib has been proven to exert significant efficacy against HER2-positive advanced breast cancer in multiple Phase III studies, and the novel ADC drug disitamab vedotin has demonstrated potent anti-tumor activity, there remains insufficient real-world data on their sequential administration. This multicenter, prospective real-world study plans to enroll 500 patients with HER2-positive advanced breast cancer receiving first-line or second-line treatment. It aims to evaluate the efficacy and safety of sequential disitamab vedotin treatment after disease progression or intolerance to pyrotinib-based regimens (first-line: pyrotinib plus trastuzumab combined with chemotherapy; second-line: pyrotinib plus capecitabine). The primary endpoint is real-world second progression-free survival (rwPFS2), while secondary endpoints cover real-world progression-free survival (rwPFS), tumor response, overall survival (OS), time to treatment failure, safety profiles and patient-reported outcomes. It is currently expected to further validate the efficacy and safety of pyrotinib in patients with advanced HER2-positive breast cancer in the real-world setting, and to evaluate the efficacy and safety of recindopril trastuzumab following pyrotinib-containing regimens.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Breast Cancer; HER2 + Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib; Drug: Trastuzumab Rezetecan

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: peng yuan; Phone Number: 86+13671287670; Email: 13671287670@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Aged ≥ 18 years old;
2. Histopathologically confirmed HER2-positive inoperable locally advanced or metastatic breast cancer;

3. Patients with first-line or second-line advanced disease:

   First-line advanced disease: no prior systemic therapy for locally advanced or metastatic disease. For patients who received neoadjuvant or adjuvant therapy, the disease-free interval (DFI) after the completion of the last chemotherapy or HER2-targeted therapy was more than 12 months; Second-line advanced disease: prior treatment with taxane combined with trastuzumab, with or without pertuzumab, in the advanced setting; or recurrence occurring during neoadjuvant/adjuvant therapy, or a disease-free interval (DFI) of ≤ 12 months after completion of the last neoadjuvant/adjuvant chemotherapy and HER2-targeted therapy;

4. Planned to receive pyrotinib-containing regimen, and judged by investigators based on clinical practice to have potential subsequent treatment with Ruikang trastuzumab after failure of pyrotinib-containing therapy;
5. Traceable medical records available throughout the treatment period.

Exclusion Criteria:

1. Failure to sign the informed consent form;
2. Pregnant or lactating females;
3. Patients participating in any interventional clinical trial involving investigational drugs or marketed drugs at enrollment;
4. Other conditions deemed ineligible for enrollment by the investigator's judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; This cohort consists of patients with first-line advanced disease. First-line advanced disease is defined as no prior systemic therapy administered for locally advanced or metastatic disease. For patients who have received neoadjuvant or adjuvant therapy, the disease-free interval (DFI) after the completion of the last chemotherapy or HER2-targeted therapy must be longer than 12 months. First-line patients receive treatment with pyrotinib plus trastuzumab combined with chemotherapy. Upon disease progression or intolerance to pyrotinib-containing regimens, subsequent treatment with Trastuzumab Rezetecan will be administered.	Drug: Pyrotinib; Pyrotinib: administered orally once daily at a dose of 400 mg, 320 mg or 240 mg within 30 minutes after breakfast. A continuous administration of 21 days is defined as one treatment cycle. The dosage of pyrotinib will be adjusted by physicians according to the individual clinical conditions. Concomitant chemotherapeutic agents and other supportive care treatments are determined at the investigators' discretion in accordance with clinical practice guidelines and drug instructions.; Drug: Trastuzumab Rezetecan; Trastuzumab Rezetecan: administered intravenously at a dose of 4.8 mg/kg on Day 1 of each cycle, with a 21-day treatment cycle.
Experimental: Cohort B; This cohort includes patients with second-line advanced breast cancer. Second-line advanced disease is defined as prior receipt of taxane combined with trastuzumab, with or without pertuzumab, in the advanced setting; or disease recurrence during neoadjuvant/adjuvant therapy, or a disease-free interval (DFI) of ≤ 12 months after completion of the last cycle of neoadjuvant/adjuvant chemotherapy and HER2-targeted therapy. Patients in the second-line setting are treated with pyrotinib plus capecitabine. Following disease progression or intolerance to pyrotinib-containing regimens, subsequent treatment with Trastuzumab Rezetecan is administered.	Drug: Pyrotinib; Pyrotinib: administered orally once daily at a dose of 400 mg, 320 mg or 240 mg within 30 minutes after breakfast. A continuous administration of 21 days is defined as one treatment cycle. The dosage of pyrotinib will be adjusted by physicians according to the individual clinical conditions. Concomitant chemotherapeutic agents and other supportive care treatments are determined at the investigators' discretion in accordance with clinical practice guidelines and drug instructions.; Drug: Trastuzumab Rezetecan; Trastuzumab Rezetecan: administered intravenously at a dose of 4.8 mg/kg on Day 1 of each cycle, with a 21-day treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rwPFS2	Second assessment of real-world progression-free survival (rwPFS2): defined as the time (in months) from the initial administration of pyrotinib-containing regimens (first-line pyrotinib combined with trastuzumab plus chemotherapy, or second-line pyrotinib combined with capecitabine) to disease progression or death after the initiation of subsequent Trastuzumab Rezetecan therapy.	From the start of first administration of pyrotinib-containing regimen (first-line or second-line) until disease progression or death occurring after the initiation of subsequent trastuzumab Rezetecan therapy，assessed up to 60 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rwPFS	Real-world progression-free survival (rwPFS): defined as the time from the initial initiation of pyrotinib treatment to disease progression, death, or switch to Trastuzumab Rezetecan due to intolerable toxicity.	From the start of initial pyrotinib treatment until the occurrence of disease progression, death, or switch to trastuzumab rezetecan due to intolerable toxicity，assessed up to 60 months.
OS	Overall Survival (OS): defined as the time from the initiation of the study treatment regimen to death from any cause.	From the initiation of the study treatment regimen to death from any cause，assessed up to 60 months.
rwORR	Real-world Objective Response Rate (rwORR): refers to the percentage of subjects with a best overall response of CR or PR from the initiation of the study treatment regimen until disease progression and study withdrawal, among the total number of subjects in the analysis set.	From the initiation of the study treatment regimen until disease progression or study withdrawal，assessed up to 60 months.
rwTTF	Real-world Time to Treatment Failure (rwTTF): defined as the time from the date of treatment initiation to treatment discontinuation for any reason, including but not limited to disease progression, death, adverse drug reactions/toxicity, patient preference, and initiation of subsequent-line therapy.	From the initiation of the study treatment regimen until disease progression or study withdrawal，assessed up to 60 months.

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Study Chair: wang shu, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 30, 2031
• Study Completion (Estimated): December 30, 2031

Study Registration Dates

• First Submitted: May 7, 2026
• First Submitted That Met QC Criteria: May 14, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HER2-positive breast cancer; Advanced breast cancer; pyrotinib; Trastuzumab Rezetecan
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; pyrotinib
• Other Study ID Numbers: MA-BC-RWS-141

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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