Multicenter phase 2 trial of MRI-based personlisation of neoadjuvant chemotherapy duration in HER2-positive early breast cancer

The multicenter phase 2 TRAIN-3 study in The Netherlands found that among patients receiving neoadjuvant anti-HER2 based chemotherapy for stage II-III HER2-positive breast cancer, one-third of patients with HR-negative tumors and one-sixth of patients with HR-positive tumors had pathological complete response after only three cycles of chemotherapy. Patients were referred for surgery once a complete radiological response was observed on MRI. Patients with pathological complete response completed 1 year of adjuvant trastuzumab and pertuzumab, whereas patients with residual invasive disease in the resection specimen continued chemotherapy for a total of nine cycles, followed by 14 cycles of trastuzumab emtansine. Median follow-up was 40.1 months (IQR 35.3-45.6). Three-year event-free survival (EFS) rate was 92.2% in patients with HR-negative tumors and 92.0% in patients with HR-positive tumors. Three-year EFS rate among patients receiving one to three cycles of neoadjuvant chemotherapy was 96.1% in the HR-negative group and 98.6% in the HR-positive group. Three-year EFS rates for patients receiving four to six cycles was 89.2% and 94.2%, respectively, and for patients receiving seven to nine cycles 90.6% and 85.4%, respectively. The frequency of grade 3-4 adverse events and grade 2 or worse neuropathy increased with increasing number of neoadjuvant chemotherapy cycles. The authors conclude that MRI-guided optimization of neoadjuvant chemotherapy duration was associated with favorable 3-year EFS outcomes in patients with stage II or III HER2-positive breast cancer.