Capecitabine combined with pyrotinib is the standard protocol for HR+/HER2+ advanced breast cancer after trastuzumab failure, but the incidence of grade 3 hand-foot-syndrome was 16.4%. Therefore, the search for efficient and low toxicity alternatives has become a research hotspot. Our previous basic studies have shown that ER inhibitor fulvestrant and HER2 inhibitor pyrotinib have a synergistic effect. The preliminary analysis of our prospective shows that the efficacy is close to that of capecitabine combined with pyrotinib, and the adverse events are significantly improved compared with capecitabine combined with pyrotinib. Therefore, it is necessary to further carry out a head-to-head phase III randomized controlled clinical trial to study the efficacy and safety of fulvestrant combined with pyrotinib in the treatment of HR + / HER2 + advanced breast cancer.
Hormone receptor (HR) positive and human epidermal growth factor receptor-2 (HER-2) positive breast cancer has the characteristics of mild biological behavior and slow progression. Currently, capecitabine combined with pyrotinib is the standard protocol for this kind of advanced breast cancer after trastuzumab failure, and the median progression free survival (PFS) is 11.0 months. The incidence of grade 3 hand-foot-syndrome was 16.4%, the incidence of grade 3 diarrhea was 30.6%, and the incidence of grade 3 myelosuppression was 6%. Therefore, the search for efficient and low toxicity alternatives has become a research hotspot. Our previous basic studies have shown that ER inhibitor fulvestrant and HER2 inhibitor pyrotinib have synergistic effect in inhibiting the proliferation of HR + / HER2 + breast cancer cells. At the same time, the preliminary analysis of our prospective, phase II, single arm study of "Fulvestrant combined with Pyrotinib in the treatment of HR + / HER2 + advanced breast cancer" shows that the efficacy is close to that of capecitabine combined with pyrotinib (median progression free survival is more than 13 months), and the adverse events are significantly improved compared with capecitabine combined with pyrotinib (grade 3 hand-foot-syndrome). This project has been supported by the "Sun-yat sun clinical research and cultivation project" of Sun-Yat Sen Memorial Hospital, Sun-Yat Sen University. Therefore, it is necessary to further carry out a head-to-head phase III randomized controlled clinical trial to study the efficacy and safety of fulvestrant combined with pyrotinib in the treatment of HR + / HER2 + advanced breast cancer, with a non-inferiority cut-off value of HR = 1.30. Combined with the analysis of biomarkers, to find the molecular indicators to predict the benefit of pyrotinib combined with endocrine therapy, so as to provide theoretical basis for guiding precise treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
516
Fulvestrant 500mg was injected intramuscularly on D1, D15, D28 and D28 Pyrotinib 400mg daily
Capecitabine 1000mg/m\^2 bid d1-d14,every 21 days Pyrotinib 400mg daily
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
RECRUITINGProgression free survival
The interval from the date of randomization to the first imaging confirmed progression of disease or death from any cause.
Time frame: 24 months
Incidence of grade 3 hand foot syndrome (rate)
From the date of enrollment to one year, the incidence of grade 3 hand-foot syndrome in the fulvestrant combined with pyrotinib group was compared with that of capecitabine combined with pyrotinib group. The incidence and severity of hand-foot syndrome were evaluated according to CTCAE 5.0 every 9 weeks (± 7 days).
Time frame: From the date of enrollment to one year
Overall survival (OS)
The time interval from the date of randomization to death due to any cause
Time frame: 50 months
Objective response rate (ORR)
According to recist1.1 standard, the proportion of patients whose best remission was CR or PR accounted for the total number of evaluable patients.
Time frame: 12 months
Clinical Benefit Rate (CBR)
According to recist1.1 standard, the proportion of patients whose best remission was CR or PR or SD ≥ 24 weeks accounted for the total number of evaluable patients.
Time frame: 12 months
Biomarkers and treatment sensitivity analysis
Cox univariate and multivariate analysis will be used to explore the correlation between endocrine and HER2 pathway related biomarkers and treatment sensitivity(The biomarkers to be analyzed included 324 tumor related genes included in the FoundationOne CDx, and ER/PR/HER2/ki67 in IHC)
Time frame: 12 months
Quality of life score
Quality of life data will be collected using the following questionnaires: FACT-B score
Time frame: 12 months
Incidence of adverse events
From the date of enrollment to one year, the incidence of adverse events in the fulvestrant combined with pyrotinib group was compared with that of capecitabine combined with pyrotinib group.
Time frame: from the date of enrollment to one year
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