Pyrotinib as neoadjuvant therapy for HER2+ breast cancer: A multicenter, randomized, controlled, phase II trial.

574 Background: Pyrotinib is a new irreversible tyrosine kinase inhibitor (TKI) which significantly improved the progression-free survival (PFS) of patients with HER2+ metastatic breast cancer (MBC). In this study we aim to investigate the efficacy and safety of pyrotinib in neoadjuvant therapy. Methods: This is an open-label, multicenter, randomized controlled trial. Eligible patients (pts) aged 18–70 years with invasive carcinoma, cT 2-3 N 0-3 M0 stage, HER2-positive breast cancer were included. We randomized 34 pts into the treatment group and 33 into the controlled group from 2019-2021. Pts in the treatment group received 6 cycles of pyrotinib 400mg + trastuzumab 6mg/kg (LD 8mg/kg) + docetaxel 75mg/m 2 + carboplatin (AUC = 6mg/ml·min) (TCbH+Py) treatment while the controlled group received 6 cycles of trastuzumab 6mg/kg (LD 8mg/kg) + docetaxel 75mg/m 2 + carboplatin (AUC = 6mg/ml·min) (TCbH). Total pathologic complete response (tpCR) was defined as no invasive or in situ disease in the breast or axilla (ypT0/Tis, ypN0) and was assigned to be the primary outcome (NCT03756064). Results: 51 cases had completed 6 cycles of neoadjuvant therapy and successfully underwent operation (21 in the treatment group and 30 in the controlled group). In the treatment group, 6 cases have not complete neoadjuvant therapy, 6 cases quitted because of poor compliance and 1 patient has not receive operation yet. For controlled group, 3 patients have not complete neoadjuvant therapy. The tpCR rate in the treatment group is 71.4% (15/21) versus 36.7% (11/30) in the controlled group. A significant difference was determined between the two groups (p < 0.05). All pts achieved an objective response in the treatment group while in the controlled group for about 83.3% (25/30). 4 cases showed stable disease (SD) and 1 case was evaluated as progressive disease (PD) in the controlled group. The most common AE in the treatment group is diarrhoea with grade 3 occurred in 6 cases (28.6%), most of this event limited in the first treatment cycle. In the controlled group 3 pts (10%) occurred grade 3 diarrhoea. Conclusions: In this study TCbH+Py neoadjuvant therapy significantly improved the tpCR rate of HER2+ breast cancer pts for about twice higher than TCbH with a manageable safety. Clinical trial information: NCT03756064.