Randomized phase 2 trial of neoadjuvant SHR-A1811 with or without pyrotinib for locally advanced or early HER2-positive breast cancer

A standard neoadjuvant regimen for HER2-positive breast cancer (BC) is nab-paclitaxel combined with carboplatin, trastuzumab, and pertuzumab (PCbHP). SHR-A1811 is a novel third-generation HER2-directed antibody-drug conjugate (ADC). A randomized phase 2 trial at Fudan University (Shanghai, China) evaluated neoadjuvant SHR-A181 for stage II or III HER2-positive BC. Patients were randomized 1:1:1 to SHR-A1811 monotherapy, SHR-A1811 plus pyrotinib, or PCbHP for 24 weeks in the neoadjuvant setting. Primary endpoint was pathological complete response (pCR) rate. There were no significant differences in pCR rate between the three groups. Grade 3 or higher treatment-related adverse events occurred in 44.8% of patients with SHR-A1811 monotherapy, 71.6% with SHR-A1811 plus pyrotinib, and 38.8% with PCbHP. There were no grade 5 TRAEs. The authors conclude that the novel third-generation HER2-directed ADC SHR-A1811 showed robust activity, with a tolerable safety profile.