ASCO 2023: Novel Antibody-Drug Conjugate Shows Clinical Activity in Metastatic Breast Cancer

By: Joshua D. Madera, MD
Posted: Tuesday, June 20, 2023

The use of the antibody-drug conjugate HER3-DXd in patients with HER2-positive and triple-negative breast cancers showed clinical efficacy across all HER3 biomarker expression levels, according to the results of a phase II study (ClinicalTrials.gov identifier NCT04699630) presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 1004). Although the favorable safety profile of HER3-DXd also seems to make it a suitable therapeutic alternative, additional investigative efforts are warranted, according to Erika P. Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, and colleagues.

A total of 60 patients with HER2-negative (68%) and triple-negative metastatic breast cancers (32%) were recruited for the study. All patients had received previous endocrine therapy, and 48% had received a CDK4/6 inhibitor. Pretreatment tissue samples from 47 patients were collected to quantify a baseline of biomarker expression used to measure progression-free survival. All patients received HER3-DXd treatment and were followed to observe their outcomes.

The study authors identified HER3 expression of more than 75% in 64% of patients, of between 25% and 74% in 28% of patients, and less than 25% in 8% of patients. In addition, a 48% clinical benefit rate and a 35% objective response rate were reported for all patients. When stratified by the quantity of HER3 expression, patients with HER3 expression of more than 75% had a clinical benefit rate of 50% and an objective response rate of 33%; patients with HER3 expression of between 25% and 74% had a clinical benefit rate of 54% and an objective response rate of 46%. Furthermore, at the 6-month interval, the progression-free survival rate was 60% for all patients, 50% for patients with HER3 expression of more than 75%, and 70% for patients with HER3 expression of between 25% and 74%. Moreover, 32% of patients experienced grade 3 or greater treatment-related adverse events, including nausea (50%), fatigue (45%), diarrhea (37%), vomiting (32%), anemia (30%), and alopecia (30%).

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2023 ASCO Annual Meeting