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.
Study Methodology
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.
Study Results
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%.
KEY POINTS
- T-DXd demonstrated durable objective responses in patients with HER2-positive breast cancer who had previously received T-DM1, trastuzmab, pertuxumab, and other HER2-targeted regimens.
- The overall response rate in 184 patients who had received T-DXd was 60.9%, with 6% achieving complete responses and 54.9% experiencing partial responses.
- The median progression-free survival was 16.4 months.
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.
Clinical Significance
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.
