A phase II clinical study investigating [fam-] trastuzumab deruxtecan (T-DXd) in patients with metastatic HER2-positive breast cancer previously treated with trastuzumab emtansine (T-DM1) showed patients had an overall response rate of 60.9% with the treatment. The study by Krop et al was presented at the 2019 San Antonio Breast Cancer Symposium (Abstract GS1-03).
T-DXd is an antibody-drug conjugate with a HER2 antibody, peptide-based cleavable linker, and a novel topoisomerase 1 inhibitor payload. Data from a previous phase I trial showed that T-DXd yielded an objective response rate of 59% in patients with advanced HER2-positive breast cancer who had been previously treated with T-DM1. The U.S. Food and Drug Administration granted priority review to T-DXd in October 2019.
In this phase II study, the researchers enrolled 253 patients with metastatic HER2-positive breast cancer previously treated with T-DM1. The trial had three parts: I, IIa, and IIb. Overall, 184 patients received the recommended phase II dose of 5.4 mg/kg of T-DXd. The patients, all of whom were women, had a median age of 55 years, and had received a median of six prior treatments for advanced disease, including trastuzumab, T-DM1, pertuzumab, and other HER2-targeted regimens.
The overall response rate in the 184 patients who received the recommended phase II dose was 60.9%, with 6% experiencing complete responses and 54.9% experiencing partial responses. The median progression-free survival was 16.4 months. The disease control rate in these patients was 97%.
Most patients—99%—experienced treatment-emergent adverse events, with 57% experiencing treatment-emergent adverse events of grade 3 or higher, including decreased neutrophil count, nausea, anemia, decreased lymphocyte count, and fatigue. Fifteen percent of the patients discontinued treatment as a result of these treatment-related adverse events. Fifteen patients (8.2%) had interstitial lung disease adjudicated as being related to T-DXd by an independent adjudication committee; interstitial lung disease was primarily grade 1 or 2 (6.0%; no grade 3 or 4; 2.2% grade 5). Additional follow-up of this data will be presented during the San Antonio Breast Cancer Symposium.
“Overall, T-DXd treatment demonstrated clinically meaningful and durable activity in a heavily pretreated patient population with HER2-positive metastatic [breast cancer]. T-DXd had a generally manageable safety profile, with ILD identified as a risk warranting proactive awareness and management,” concluded the study authors.
Ian Krop, MD, PhD
“The high rate of durable responses observed with [T-DXd] in patients whose cancers had progressed on T-DM1 and other therapies suggests this agent could provide a new treatment option for this patient population,” said Ian Krop, MD, PhD, Associate Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and lead author of this study, in a statement. “Thus, there clearly is an unmet medical need for new and improved therapies for such patients.”
Disclosure: The study was funded by Daiichi Sankyo and AstraZeneca. For full disclosures of the study authors, visit abstractsonline.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.