Investigational Drug Candidate Shrinks HER2-Low Breast Tumors, but Complete Response Rate Is About 3%

Preoperative treatment with the investigational anticancer drug SHR-A1811 produced marked tumor shrinkage in patients with HER2-low breast cancer, but the complete response rate was low.

According to Chinese outlet Bioon on the 23rd (local time), a research team led by Professor Liu Zhenzhen of Zhengzhou University published results from a phase 2 trial of neoadjuvant SHR-A1811 in patients with hormone receptor-positive, HER2-low (HR+/HER2-low) breast cancer in the journal Nature Communications.

The researchers enrolled 66 previously untreated patients ages 18 to 70 with HR+/HER2-low invasive breast cancer and administered SHR-A1811 intravenously at 6.4 mg/kg every 3 weeks for a total of eight doses.

The objective response rate (ORR) among the 65 patients included in the efficacy analysis was 81.5%, exceeding the prespecified threshold of 66.0% set in the trial design.

By contrast, only two patients (3.1%) achieved a pathologic complete response (pCR), meaning their tumors had completely disappeared. Just six patients (9.2%) had a residual cancer burden score of 0 or 1.

In terms of safety, 37.9% of all patients experienced treatment-related adverse events of grade 3 or higher. The most common severe adverse events were neutropenia (27.3%), leukopenia (16.7%) and anemia (13.6%).

No treatment-related deaths or cases of interstitial lung disease were reported.

SHR-A1811 is an anti-HER2 antibody-drug conjugate (ADC) with a drug-to-antibody ratio (DAR) of 5.7. In a previous study in patients with metastatic HER2-low breast cancer, it had an objective response rate of 60.4% and an interstitial lung disease incidence of 2.6%.

The researchers said single-agent neoadjuvant SHR-A1811 could achieve "an ideal tumor response rate, with adverse events at a manageable level" and could be an alternative neoadjuvant treatment for HR+/HER2-low breast cancer.

However, they added that large randomized controlled trials are needed to comprehensively validate its clinical value. Survival follow-up is ongoing.