Neoadjuvant SHR-A1811 Demonstrates Promise for Patients With HER2-Positive Breast Cancer

According to results from the phase 2 FASCINATE-N trial, neoadjuvant SHR-A1811 with or without pyrotinib demonstrated promising efficacy and safety among patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced or early breast cancer. 

“Taxane plus platinum combined with trastuzumab and pertuzumab remains the preferred choice according to the National Comprehensive Cancer Network (NCCN) guidelines,” stated Junjie Li, MD, University Shanghai Cancer Center, Shanghai, China, and coauthors. “The emergence of new HER2-targeted therapies, including HER2-directed antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs), have revolutionized the treatment in metastatic HER2-positive breast cancer.” 

In this open-label study, 265 patients with stage 2/3 HER2-positive breast cancer were randomized on a 1-to-1-to-1 basis to receive SHR-A1811 monotherapy (n = 87), SHR-A1811 plus pyrotinib (n = 88), or nab-paclitaxel plus carboplatin, trastuzumab, and pertuzumab (n = 90) for up to 24 weeks or until disease progression or unacceptable toxicity. The primary end point was pathological complete response (pCR) rate. A key secondary end point was safety. 

At analysis, the pCR rate was 63.2% in the SHR-A1811 monotherapy arm, 62.5% in the SHR-A1811 plus pyrotinib arm, and 64.4% in the chemotherapy arm. Grade ≥3 treatment-related adverse events occurred in 44.8% of patients in the SHR-A1811 monotherapy arm, 71.6% of patients in the SHR-A1811 plus pyrotinib arm, and 38.8% of patients in the chemotherapy arm. No treatment-related deaths occurred.

“This is the first study to report the efficacy and safety of third-generation HER2-directed ADC in the neoadjuvant setting for HER2-positive breast cancer,” concluded Dr Li et al. “The development of ADCs provides a promising avenue for the further treatment of HER2-positive breast cancer.” 

Source:

Li JJ, Wang ZH, Chen L, et al. Efficacy and safety of neoadjuvant SHR-A1811 with or without pyrotinib in women with locally advanced or early HER2-positive breast cancer: A randomized, open-label, phase 2 trial. Ann Oncol. Published online: March 4, 2025. doi: 10.1016/j.annonc.2025.02.011