Pyrotinib Combined With Trastuzumab and AI in the First-line Treatment of HER2 Positive/ HR Positive MBC

This study is a randomized, open-label, phase II study, comparing the efficacy and safety of trastuzumab plus aromatase inhibitors, with or without pyrotinib, in the treatment of HR (hormone receptor)+/HER2 (human epidermal growth factor receptor 2) + MBC and inoperable LABC patients.

This is a randomized, two-arm, open-label, multicenter phase II trial. Our primary purpose is to compare that PFS of patients with trastuzumab, AI plus pyrotinib and trastuzumab plus an AI for HER2-positive and hormone receptor-positive MBC or locally advanced breast cancer (LABC).

Eligible patients will randomized to a ratio of 1:1 to pyrotinib+ trastuzumab + aromatase inhibitor (experimental group) or trastuzumab+aromatase inhibitor (control group). Stratification factors were 1)time since adjuvant hormone therapy (\<=12 months/\>12 months/no prior hormone therapy); 2) lesion (visceral; non-visceral).

In treatment period, patients will be administrated trastuzumab plus aromatase inhibitors, with or without pyrotinib, every 21 days for 1 cycle, until disease progression, toxicity intolerance, withdrawal of informed consent, patients judged must be terminated study termination.

The imaging evaluation was performed according to the RECIST 1.1 criteria every 6 weeks.

Eligibility Criteria:
Inclusion Criteria:

1. Age≥18 years, female;
2. Postmenopausal or pre-menopausal with ovarian function suppression;
3. At least one measurable lesion evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1;
4. Metastatic or inoperable local advanced breast cancer;
5. HER2-positive breast cancer;
6. HR-positive breast cancer;
7. LVEF ≥50%;

Exclusion Criteria:

1. Previous systemic non-hormonal anticancer therapy in the metastatic or advanced breast cancer setting;
2. Received endocrine therapy within 7 days before randomization;
3. Uncontrolled central nervous system metastases;
4. Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months.
5. Other malignancies within the last 3 years, except for carcinoma in situ of the cervix or basal cell carcinoma.
6. Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
7. Severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease, which leading to a clinical indication for chemotherapy.
8. History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia);
9. History of myocardial infarction within 6 months of randomization
10. History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
11. Pregnant or lactating women;
12. QT interval\>470 ms；
13. Serious concomitant diseases (including severe hypertension, severe diabetes, active infection, thyroid disease, etc.) that are harmful to the patient's safety or affect the patient's completion of the study;