117P Three-year invasive disease-free survival results from a phase II study of pyrotinib plus trastuzumab and albumin-bound paclitaxel as neoadjuvant treatment in HER2-positive early or locally advanced breast cancer

Our previous phase II study (NCT04152057) revealed that the triple combination regimen of pyrotinib plus albumin-bound paclitaxel and trastuzumab significantly promoted the pathological complete response (pCR) rate in early and locally advanced HER2-positive breast cancer (BC). Here, we further assessed the 3-year invasive disease-free survival (iDFS) of addition pyrotinib to trastuzumab and albumin-bound paclitaxel in HER2-positive early or locally advanced BC in the neoadjuvant setting. Details of the trial design and study population have been previously reported. In brief, eligible patients were assigned to receive 4 cycles of neoadjuvant pyrotinib, trastuzumab, and albumin-bound paclitaxel. After surgery, patients were scheduled to be given 4 cycles of adjuvant anthracycline plus cyclophosphamide, followed by HER2-targeted therapy at the physician's discretion, adjuvant irradiation, and endocrine therapy, if applicable. Here, we reported the secondary endpoint of 3-year iDFS, defined as the duration from treatment initiation to the occurrence of iDFS events, including death from any cause and invasive ipsilateral breast tumor recurrence or progression. As of June 20, 2023, the median follow-up period was 45.0 months (IQR: 23.1, 47.6) and the rate of 3-year iDFS was 93.8%. Two women suffered iDFS events during follow-up. One patient with HR-negative disease who achieved pCR developed lung metastasis at the follow-up of 42.02-month, and another patient who having non-pCR HR-positive BC occurred brain metastasis at the follow-up of 22.62-month. Both of them received 4 cycles of anthracycline-based adjuvant chemotherapeutics plus trastuzumab. Although not statistically different, we observed a trend of iDFS benefit among patients who achieved pCR. Compared to the dual-HER2 blockades, adding pyrotinib to the combo regimen of chemotherapy and trastuzumab further improved the pCR rate which consequently translates to the iDFS benefit in non-metastatic BC, justifying the rationality of synergizing small molecule tyrosine kinase inhibitors, trastuzumab, and chemotherapy.