By: Charles Bankheadmetastatic
From: medpagetoday.com
The FDA expanded the approval of trastuzumab deruxtecan (T-DXd, Enhertu) to include treatment of unresectable/metastatic hormone receptor (HR)-positive, HER2-low/ultralow breast cancer.
Approval stipulates use in patients with disease that has progressed on or proven unresponsive to at least one prior endocrine therapy in the metastatic setting, according to a statementopens in a new tab or window from drugmakers AstraZeneca and Daiichi Sankyo.
“Endocrine therapy is typically used in the initial treatment of HR-positive metastatic breast cancer and following progression, subsequent chemotherapy is associated with poor outcomes,” said Aditya Bardia, MD, MPH, of the UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, in the statement. “With a median progression-free survival [PFS] exceeding 1 year and a response rate of more than 60%, trastuzumab deruxtecan offers a potential new standard of care for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer following endocrine therapy.”
Experience with T-DXd in clinical practice has been consistent with clinical trial results, including patients with HER2-ultralow breast cancers, he told MedPage Today.
With the addition of a new treatment option for a new molecularly defined type of breast cancer, “it is critical for patients to understand the HER2 status of their metastatic breast cancer to help them make informed treatment decisions,” said Krissa Smith, of the Susan G. Komen advocacy organization.
HER2-ultralow is defined as immunohistochemistry (IHC) 0 with membrane staining.
T-DXd, an antibody-drug conjugate now approved for multiple tumor types, gained approvalopens in a new tab or window in 2022 for unresectable or metastatic HER2-low breast cancer — defined by an FDA-approved test as IHC 1+ or IHC 2+/in situ hybridization (ISH)‑. This approval included patients who had received chemotherapy in the metastatic setting or developed recurrence during or within 6 months of completing adjuvant chemotherapy.
Bardia emphasized that conventionally defined HER2-negative breast cancers (by IHC) still have some level of HER2 expression.
“The HER2 assay was developed to identify tumors with high expression of HER2, and that was defined operationally as HER2 high,” he said. “But it was very clear from the get-go, 20 or 30 years ago, that even in the HER2-negative tumors there was some HER2 expression. We need to emphasize that HER2-negative does not mean there is no HER2 expression.”
Accurate assessment of HER2 expression prior to starting treatment is essential, Bardia continued. The FDA has specified use of the Ventana Pathway anti-HER2/neu (4B5) antibody assay. Additionally, the American Society for Clinical Pathology has guidelines for testing for HER2.
Support for the new approval came from the randomized phase III DESTINY-Breast06opens in a new tab or window trial involving patients with endocrine-resistant/refractory, inoperable or metastatic HR-positive breast cancer with HER2-low or HER2-ultralow expression. Investigators in the international trial randomized and treated 866 patients with either T-DXd or physician’s choice of chemotherapy.
The primary analysis showed a median PFS of 13.2 months with T-DXd and 8.1 months with chemotherapy, representing a 36% reduction in the hazard ratio for disease progression or death (95% CI 0.54-0.76, P<0.0001). In an exploratory analysis, results were seen to be consistent between patients with HER2-low expression and HER2-ultralow expression.
HER2 status in the trial was confirmed by a central laboratory, which showed that 85-90% of tumors classified as HR-positive/HER2-negative subsequently were found to have actionable levels of HER2 expression, according to the statement.
The safety profile of T-DXd in DESTINY-Breast06 was consistent with previous clinical trials of the drug in breast cancer with no new safety concerns identified.
T-DXd is also approved for HER2-positive (IHC 3+ or ISH+) breast canceropens in a new tab or window, non-small cell lung cancer, gastric or gastroesophageal junction cancers, and carries a tumor-agnostic indicationopens in a new tab or window for HER2-positive cancers as well.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.