Enhertu’s label expansion comes on the heels of the FDA’s approval of the partners’ Datroway for a related type of breast cancer.
The FDA on Monday agreed to a proposed label expansion of AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu (fam-trastuzumab deruxtecan-nxki), opening up wider use of the drug in breast cancer.
Previously, Enhertu could not be used to treat HER2-ultralow patients. With this expansion, the ADC can now be used in patients with unresectable or metastatic breast cancer and who are HR-positive and HER2-low or HER2-ultralow. HER2 is a key breast cancer biomarker. Patients with higher expression levels of the protein tend to progress more rapidly than HER2-negative counterparts, but also respond more readily to HER2-targeted therapies.
According to Monday’s news release, Enhertu is now the first HER2-directed therapy approved for HER2-low and HER2-ultralow metastatic breast cancer in patients whose disease has progressed after at least one prior line of endocrine therapy.
The label expansion will bring Enhertu “to an earlier treatment setting and a broader patient population with HER2 expressing metastatic breast cancer” Dave Fredrickson, executive vice president of AstraZeneca’s Oncology Hematology Business Unit, said in a statement.
The FDA’s decision on Monday was backed by data from the Phase III DESTINY-Breast06 trial, in which Enhertu elicited a 36% drop in the risk of disease progression or death compared to chemotherapy. In the study’s patient population of chemotherapy-naïve metastatic breast cancer patients with HR-positive and HER2-low or HER2-ultralow disease, Enhertu additionally yielded a confirmed objective response rate (ORR) of 62.6%, whereas chemotherapy counterparts only saw an ORR of 34.4%.
In an exploratory analysis, Enhertu treatment improved progression-free survival by 24% in those with HER2-ultralow disease. AstraZeneca and Daiichi Sankyo in Monday’s press announcement called this effect “clinically meaningful,” though it fell short of statistical significance.
Patients in the DESTINY-Breast06 trial tolerated Enhertu overall, with 20% of treated patients developing serious adverse events. Common serious toxicities included interstitial lung disease (ILD), hypokalemia and febrile neutropenia, and 2.8% of patients died from treatment-related adverse events. Enhertu’s label carries a boxed warning for ILD and embryo-fetal toxicity.
Enhertu’s label expansion on Monday comes just days after AstraZeneca and Daiichi Sankyo won another ADC approval from the FDA. Datroway—previously known as Dato-DXd—recently secured the agency’s go-ahead for use in unresectable or metastatic HR-positive and HER2-negative breast cancer. The companies are also proposing the use of Dato-DXd for non-small cell lung cancer, the decision for which is expected in the third quarter of this year.
