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William J. Gradishar, MD, FACP, FASCO


ASCO 2022: Novel HER3-Directed Antibody-Drug Conjugate Under Study in Metastatic Breast Cancer

By: Jenna Carter, PhD
Posted: Tuesday, June 14, 2022

Safety and efficacy updates on the use of patritumab deruxtecan in patients with HER3-expressing metastatic breast cancer were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 1002). According to Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute, Boston, and colleagues, this novel HER3-directed antibody-drug conjugate showed activity in patients with hormone receptor–positive, HER2-negative, and HER2-positive metastatic breast cancer as well as in patients with triple-negative metastatic breast cancer, with “adequate safety and tolerability.”

A total of 182 patients with HER3-expressing metastatic breast cancer were included in this phase III, multicenter, open-label study. Patients were enrolled in a dose-escalation phase (3.2–8.0 mg/kg intravenously every 3 weeks) and dose-finding portions across molecular subtypes (n = 66; including 14 with HER2-positive disease). This was followed by dose expansion in the following subtypes: HER3-high (4.8 mg/kg, n = 33, or 6.4 mg/kg, n = 31); HER3-low (6.4 mg/kg, n = 21); and hormone receptor–positive, HER2-negative, or HER3-high triple-negative disease (6.4 mg/kg, n = 31). The primary objective was to assess safety and efficacy, with secondary objectives to determine the relationship between efficacy and HER3 expression.

The median treatment duration with patritumab deruxtecan was 5.9 months (range = 0.7–30.6 months). A pooled evaluation of dose-escalation and -expansion data revealed efficacy in patients with hormone receptor–positive, HER2-negative metastatic, and triple-negative disease, as well as in those with HER2-positive disease. Additionally, a total of 130 patients (71.4%) had grade 3 or higher adverse events, the most common being a decreased neutrophil count

Based on these results, the authors concluded that this longer follow-up safety profile was consistent with previous reports of adequate safety and tolerability. They also reported that ongoing studies are focused on specific biomarkers and their association with efficacy.

Disclosure: For full disclosures of the study authors, visit

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