FDA Approves AstraZeneca/Daiichi Sankyo’s ADC Enhertu for Second-Line Treatment of HER2-Positive Metastatic Breast Cancer

Today, the FDA’s official website showed that the FDA has approved the expanded indication of Enhertu (trastuzumab deruxtecan), an antibody-drug conjugate (ADC) jointly developed by AstraZeneca and Daiichi Sankyo, for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have previously received a HER2-targeted therapy.

Breast cancer is the most common cancer globally, with over 2 million confirmed cases in 2020, leading to nearly 685,000 deaths worldwide. Approximately one in five breast cancer cases are considered HER2-positive. HER2 is a tyrosine kinase receptor pro-growth protein expressed on the surface of various types of tumors, including breast cancer, gastric cancer, lung cancer, and colorectal cancer. Overexpression of the HER2 protein may result from HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer. Patients with HER2-positive metastatic breast cancer often experience disease progression after initial treatment, necessitating additional treatment options to further delay disease progression and prolong patient survival.

Image Source: FDA Official Website

Enhertu is an ADC therapy jointly developed by AstraZeneca and Daiichi Sankyo. It is designed using Daiichi Sankyo's proprietary DXd ADC technology platform and consists of a humanized monoclonal antibody targeting HER2 connected to a topoisomerase 1 inhibitor payload via a cleavable tetrapeptide linker.

This approval was based on data from the pivotal phase 3 clinical trial DESTINY-Breast03. In the trial, Enhertu reduced the risk of disease progression or death by 72% ([HR]=0.28; 95% CI: 0.22-0.37) compared to the active control group in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. According to the assessment by blinded independent central review (BICR), the median progression-free survival (PFS) for patients treated with Enhertu had not yet been reached (95% CI: 18.5-NE), while it was 6.8 months (95% CI: 5.6-8.2) for the active control group.

Enhertu showed a clear trend toward improved overall survival (OS) (HR=0.56; 95% CI: 0.36-0.86), but the analysis is not yet mature and has not reached statistical significance.

Beyond second-line treatment for HER2-positive breast cancer patients, the supplemental Biologics License Application (sBLA) for Enhertu to treat patients with unresectable or metastatic non-small cell lung cancer (NSCLC) harboring HER2 mutations who have been previously treated has received Priority Review designation from the FDA. Recently, it also received Breakthrough Therapy Designation from the FDA for the treatment of patients with unresectable or metastatic breast cancer with low HER2 expression. We look forward to this groundbreaking therapy benefiting more patients.

References:

[1] Enhertu FDA label. Retrieved May 4, 2022, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761139s017s020lbl.pdf

▽Follow 【WuXi AppTecGermany】WeChat Official Account