In this episode, Aakash Desai, MD; Narjust Florez, MD; and Paolo Tarantino, MD, discuss the biologic rationale and clinical development of agents targeting HER3 for the treatment of breast and lung cancers. The potential niche for HER3-targeted agents in these treatment landscapes is considered, with consideration of acquired resistance to previous targeted therapies and parallels to other approved antibody–drug conjugates. Their conversation covers clinical trial data from:

• Phase I/II study of patritumab deruxtecan in HR-positive/HER2-negative or triple-negative metastatic breast cancer, published by Krop and colleagues in the Journal of Clinical Oncology 
• BRE-354: A phase II study of patritumab deruxtecan in several subtypes of previously treated advanced/metastatic breast cancer, presented at ASCO 2023
• ICARUS-Breast01: A phase II study of patritumab deruxtecan in patients with HR-positive/HER2-negative or HER2-low advanced breast cancer, presented at the ESMO Breast Cancer Congress 2023
• SOLTI-TOT-HER3: A window-of-opportunity study of neoadjuvant patritumab deruxtecan for treatment-naive HER2-negative early stage breast cancer, presented at the ESMO Breast Cancer Congress 2023
• HERTHENA-Lung01: A phase II study of patritumab deruxtecan in in patients with EGFR-mutated NSCLC after treatment with osimertinib and platinum-based chemotherapy, presented at the World Conference on Lung Cancer 2023
• HERTHENA-Lung02: An ongoing phase III study of patritumab deruxtecan vs platinum-based chemotherapy after osimertinib for the treatment of EGFR-mutated NSCLC
• eNRGy: A phase I/II study of the bispecific HER2 x HER3 antibody zenocutuzumab in multiple solid tumor types with NRG1 gene fusion, presented at ASCO 2022
• DESTINY-Breast04: A phase III study of trastuzumab deruxtecan for the treatment of patients with HER2-low metastatic breast cancer, published by Modi and colleagues in the New England Journal of Medicine
• DAISY: A phase II trial of  trastuzumab deruxtecan for the treatment of breast cancer with variable levels of HER2 expression including HER2-low and HER2-zero, published by Mosele and colleagues in Nature Medicine 

Presenters:

Aakash Desai, MD
Affiliation awaiting contract

Narjust Florez, MD
Associate Director of The Cancer Care Equity Program
Thoracic Medical Oncologist, Dana-Farber Cancer Institute
Assistant Professor of Medicine, Harvard Medical School
Boston, Massachusetts

Paolo Tarantino, MD
Advanced Research Fellow
Breast Oncology Center
Dana-Farber Cancer Institute
Boston, Massachusetts
Content based on an online CME program supported by an independent educational grant from Daiichi Sankyo, Inc.

Link to full program: https://bit.ly/45UYsw3