A HER2-targeted regimen produced high pathologic complete response rates before surgery in patients with locally advanced HER2-positive breast cancer, according to results from a single-arm phase II neoadjuvant trial conducted in China. The research was highlighted in a media briefing ahead of the 2026 ASCO Breakthrough Meeting, taking place June 25 to June 27 in Singapore.
The prospective, multicenter trial enrolled 124 patients with stage II to III nonmetastatic HER2-positive breast cancer and high tumor burden across seven centers in China. Patients received neoadjuvant inetetamab, pyrotinib, docetaxel, and carboplatin (neoPICD) for 18 weeks, followed by surgery 2 to 4 weeks later. Patients then continued inetetamab and pyrotinib to complete 1 year of anti-HER2 treatment.
Inetetamab is a HER2-targeted monoclonal antibody designed to enhance antibody-dependent cellular cytotoxicity, and pyrotinib is an oral irreversible pan-HER tyrosine kinase inhibitor targeting HER1, HER2, and HER4. Both drugs were developed in China and are not approved by the U.S. Food and Drug Administration.
“This regimen demonstrates favorable efficacy and a manageable safety profile, offering a better option for patients with locally advanced disease with high tumor burden, thereby addressing a critical unmet need in the current treatment landscape,” said study author Chenghui Yang, PhD, of the Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Study Details
Among 108 patients evaluable for efficacy, the total pathologic complete response rate was 60.2%, indicating no active cancer cells were found in surgically removed breast and lymph node tissue. The breast pathologic complete response rate was 65.7%, the objective response rate was 92.6%, and the disease control rate was 100%.
Responses appeared more pronounced among patients with hormone receptor–negative tumors. The total pathologic complete response rate was 73.3% among patients with hormone receptor–negative disease vs 43.8% among those with hormone receptor–positive disease. Breast pathologic complete response rates were 76.7% vs 52.1%, respectively.
The most common adverse events were diarrhea, anemia, nausea/vomiting, and decreased appetite. No treatment-related deaths occurred.
Longer follow-up is planned to evaluate survival outcomes, including overall survival. The researchers also noted that a larger phase III randomized trial comparing inetetamab plus pyrotinib with trastuzumab/pertuzumab-based treatment may be considered.
Expert Perspective
“This study highlights a promising new HER2-targeted combination that achieved notably high pathologic complete response rates in patients with locally advanced HER2-positive breast cancer. While these results are encouraging, particularly for patients with high tumor burden and hormone receptor-negative disease, they come from a single-arm phase II trial,” said Rebecca Alexandra Dent, MD, Deputy Chief Executive Officer (Clinical) and Senior Consultant at the National Cancer Centre Singapore and an ASCO Expert in breast cancer. “Randomized studies comparing this approach with current standards, such as trastuzumab and pertuzumab-based regimens as well as the more recently approved [fam-trastuzumab deruxtecan-nxki], will be essential before this strategy can be widely adopted.”
Disclosures: Funding for this study was provided by Wenzhou Medical University. For full disclosures of the study authors, visit coi.asco.org.
