Neratinib is an irreversible pan-HER tyrosine kinase inhibitor (TKI). Currently, no studies have investigated the use of macromolecular anti-HER2 agents combined with TKIs for the treatment of non-pCR HER2-positive breast cancer following neoadjuvant therapy. Furthermore, there are no prospective randomized controlled trials comparing trastuzumab plus pertuzumab versus trastuzumab plus TKIs in HER2-positive breast cancer patients with residual cancer burden class (RCB) I or II after neoadjuvant trastuzumab and pertuzumab. Therefore, this study aimed to evaluate the efficacy and safety of adjuvant trastuzumab plus neratinib in patients with hormone receptor-positive/HER2-positive breast cancer and RCB 0/I following neoadjuvant trastuzumab and pertuzumab therapy.
Female patients aged 18-70 years;
Eastern Cooperative Oncology Group performance status of 0 or 1;
Clinical stage at initial diagnosis (per the 8th edition of the American Joint Committee on Cancer Staging Manual): cT1-4/N1-3/M0 (cT1mi/N0 or cT1a-b/N0 are eligible), meeting the criteria for neoadjuvant therapy as per NCCN 2022 guidelines;
Histologically confirmed hormone receptor-positive (estrogen receptor ≥1% and/or progesterone receptor ≥1%) and HER2-positive (immunohistochemistry 3+ or fluorescence in situ hybridization-positive) invasive breast cancer;
History of local or regional breast cancer recurrence;
Clinical stage IV (metastatic) breast cancer;
Bilateral breast cancer;
History of other malignant tumors within the past 5 years, except for curatively treated cervical carcinoma in situ, basal cell carcinoma, or cutaneous squamous cell carcinoma;
Parallel
Trastuzumab and neratinib
DrugTrastuzumab (8 mg/kg IV loading dose, followed by 6 mg/kg IV once every 3 weeks), and neratinib 240 mg orally once daily. The trastuzumab treatment will be continued for a total of 18 cycles, encompassing both the preoperative and adjuvant phases, while neratinib will be maintained throughout the adjuvant period.
Trastuzumab and Pertuzumab
DrugTrastuzumab (8 mg/kg IV loading dose, followed by 6 mg/kg IV once every 3 weeks), and pertuzumab (840 mg IV loading dose, followed by 420 mg IV once every 3 weeks). This regimen will be repeated for a total of 18 cycles,encompassing both the preoperative and adjuvant phases.
Invasive disease free survival, IDFS
The time from random assignment until the first occurrence of invasive disease recurrence, distant recurrence, or death from any cause.
Disease free survival, DFS
The time from random assignment until recurrence, the development of a second cancer, or death from any cause.
Overall survival, OS
The time from randomization to death from any cause.
Distant disease free survival, DDFS
The time from random assignment until the first occurrence of distant recurrence or death from any cause.
Incidence and severity of adverse events
The incidence and severity of adverse events will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).
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