Early assessment of clinical response to treatment would facilitate individualized therapy, with ineffective therapy changed. Pyrotinib is a new oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor that targets human epidermal growth factor receptor (HER) 1, HER2, and HER4. Whether the addition of pyrotinib to TCH (trastuzumab, docetaxel, carboplatin) regimen can bring benefit to non-responder after 2 neoadjuvant cycles of TCH is unclear. This prospective, open-label, multicenter study (NCT03847818) explored the efficacy and safety of neoadjuvant pyrotinib + TCH in patients with early or locally advanced HER2-positive breast cancer who did not respond after 2 neoadjuvant cycles of TCH.
Eligible patients were aged 18–70 years, with stage II-III HER2-positive invasive breast cancer. Patients received 2 cycles of TCH (docetaxel: 75 mg/m2 every 3 weeks; carboplatin: area under the curve 5; and trastuzumab: 8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) first, and those with complete/partial response continued 4 cycles of TCH (cohort A). Non-responder after 2 cycles of TCH received 4 cycles of TCH (cohort B) or pyrotinib (400 mg orally once per day) + TCH (cohort C). The primary endpoint was the proportion of patients who achieved total pathological complete response (tpCR, ypT0/is, ypN0).
From December 2018 to December 2020, a total of 66 patients were enrolled and completed the neoadjuvant therapy and surgery, including 30 patients in cohort A, 10 in cohort B, and 26 in cohort C. The tpCR rate was the highest in cohort C (34.6%), followed by 30.0% in cohort A and 10.0% in cohort B. The most common grade 3-4 adverse events were diarrhea (40.3%), vomiting (25.2%), and neutropenia (7.5%) in cohort C. No treatment-related death was observed.
This exploratory analysis demonstrated the efficacy and tolerable toxicity of pyrotinib + TCH in patients with early or locally advanced HER2-positive breast cancer who did not respond after 2 cycles of TCH in the neoadjuvant setting, and also confirmed the importance of early efficacy assessment during neoadjuvant therapy.
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All authors have declared no conflicts of interest.