The goal of this multicentre, randomized, double-blind controlled, phase III clinical trial is to compare the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab (THP) for newly diagnosed recurrent/metastatic Human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer, and to explore the impact of biomarkers on clinical efficacy and safety. The main questions it aims to answer are: * Analyse the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of THP. * Explore the impact of biomarkers on clinical efficacy and safety of the combination of disitamab vedotin in combination with pyrotinib treatment. Participants in the experimental group will receive disitamab vedotin in combination with pyrotinib for 6-8 cycles (each cycle lasting 28 days), followed by maintenance treatment with trastuzumab in combination with pyrotinib. Participants in the control group will receive paclitaxel in combination with trastuzumab and pertuzumab for 6-8 cycles (each cycle lasting 21 days), followed by maintenance treatment with trastuzumab and pertuzumab. Researchers will compare disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab to see if disitamab vedotin in combination with pyrotinib could be a new option for first-line treatment of HER2-positive metastatic breast cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
312
disitamab vedotin 2mg/kg iv q2w
pyrotinib 400mg po q28d
trastuzumab 8mg/kg for the first cycle, 6mg/kg for subsequent treatments iv q21d
pertuzumab 840mg for the first cycle, 420mg for subsequent treatments iv q21d
Docetaxel/paclitaxel/albumin paclitaxel/liposomal paclitaxel, dosage and administration are determined according to the latest version of the NCCN and CSCO breast cancer guideline recommendations
Sun Yat-sen Memorial Hospital,Sun Yat-sen University
Guangzhou, Guangdong, China
RECRUITINGProgression Free Survival (PFS)
From enrollment to progression or death (for any reason)
Time frame: Estimated 30 months
Overall Survival (OS)
From enrollment to death (for any reason)
Time frame: Estimated 8 years
Disease control rate (DCR)
Ratio of complete response (CR) , partial response (PR) and stable disease (SD) in all subjects
Time frame: Estimated 30 months
Objective Response Rate (ORR)
Ratio of CR and PR in all subjects
Time frame: Estimated 30 months
Clinical Benefit rate (CBR)
Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects
Time frame: Estimated 30 months
Adverse Events (Based on CTCAE 5.0 standards)
Safety
Time frame: From informed consent through 28 days following treatment completion
Quality of Life (QoL) by Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B)
QoL was assessed using FACT-B. FACT-B is a 37-item questionnaire with 5 subscales assessing physical, social, emotional, and functional well-being, with scores ranging from 0 to 4 for each question. Higher scores generally indicating a better quality of life.
Time frame: Estimated 30 months
Exploration of biomarkers
Next Generation Gene Sequencing (NGS) detection of tissue and blood specimens, including ERBB1/ERBB2/ERBB3/ERBB4/AKT/TP53/PIK3CA and so on. Objective to explore the correlation between biomarkers and the objective response rate (ORR), as well as progression-free survival (PFS).
Time frame: Estimated 30 months
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