AstraZeneca and Daiichi Sankyo’s ADC Enhertu Achieves Breakthrough in HER2-Low Metastatic Breast Cancer with Significant Survival Benefits

On February 21, AstraZeneca and Daiichi Sankyo announced that Enhertu, an antibody-drug conjugate (ADC) jointly developed by the two companies, achieved positive results in the pivotal phase 3 trial DESTINY-Breast04. The data showed that Enhertu significantly improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy in patients with HER2-low, unresectable and/or metastatic breast cancer, regardless of the patients' hormone receptor (HR) status. According to the press release, this is the first phase 3 result for Enhertu in HER2-low, metastatic breast cancer patients.

Public information shows that Enhertu (trastuzumab deruxtecan, DS-8201) is an ADC drug designed using Daiichi Sankyo's proprietary DXd ADC technology platform. It links the human HER2 antibody trastuzumab via a tetrapeptide linker to a novel topoisomerase 1 inhibitor, targeting cancer cells and delivering the drug inside the cells. Previously, Enhertu has been approved by the FDA as a third-line treatment for patients with HER2-positive unresectable or metastatic HER2-positive breast cancer who have been previously treated, as well as for patients with HER2-positive locally advanced or metastatic gastric cancer and gastroesophageal junction (GEJ) adenocarcinoma who have received trastuzumab-based therapy.

The DESTINY-Breast04 trial, recently published, is a global, randomized, open-label, registrational Phase 3 trial designed to evaluate the efficacy and safety of Enhertu (5.4 mg/kg) compared to chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel) in patients with HER2-low, unresectable and/or metastatic breast cancer. All patients in the trial underwent HER2 testing and had previously received one or two chemotherapy regimens.

Patients in the trial were randomized 2:1 to receive Enhertu or chemotherapy. The primary endpoint was PFS in patients with HR-positive disease based on blinded independent central review (BICR). Key secondary endpoints included PFS based on BICR for all patients (regardless of HR status), OS for patients with HR-positive disease, and OS for all patients.

Source of image: Daiichi Sankyo official website

Results showed that DESTINY-Breast04 met its primary endpoint, with Enhertu demonstrating superior PFS in previously treated HR-positive, HER2-low metastatic breast cancer patients compared to standard chemotherapy. Regardless of the HR status (HR-positive or HR-negative), the trial achieved the key secondary endpoint of PFS. The trial also reached the key secondary endpoints of OS in HR-positive disease patients and OS in all patients. Additionally, the safety profile of Enhertu observed in this study was consistent with previous clinical trials, with no new safety issues identified.

Breast cancer is one of the most common cancers among women worldwide and a leading cause of cancer-related deaths in women. Statistics show that approximately 20% of breast cancer cases are HER2-positive. The expression of HER2 on the surface of cancer cells is associated with disease progression and poor prognosis. Several drugs targeting HER2 have been approved, benefiting patients with HER2-positive metastatic breast cancer and improving their survival rates.

However, about 80% of breast cancer cases are classified as HER2-negative, and more than 40% of these cases involve cancer cells that express HER2 at low levels as surface antigens. For these HER2-low tumors, there are currently no approved antibody therapies. Existing clinical guidelines classify such patients as HER2-negative for treatment purposes, and many patients eventually run out of available treatment options after making some progress with current therapies.

Hope the ADC product jointly developed by AstraZeneca and Daiichi Sankyo makes more progress in clinical research, and brings clinical benefits to more cancer patients as soon as possible.

References:

[1]Enhertu significantly improved both progression-free and overall survival in DESTINY-Breast04 trial in patients with HER2-low metastatic breast cancer , Retrieved February 21, 2022, from https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-improves-pfs-and-os-in-her2-low-bc.html

(Original text has been abridged)

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