On February 24, 2023 AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) reported that it has been approved in China as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens (Press release, AstraZeneca, FEB 24, 2023, View Source [SID1234627687]).

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Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The approval by China’s National Medical Products Administration (NMPA) is based on the results of the DESTINY-Breast03 Phase III trial, where Enhertu demonstrated a 72% reduction in the risk of disease progression or death compared to trastuzumab emtansine (T-DM1) (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.22-0.37; p<0.000001) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

In China, breast cancer is the most common cancer in women, with more than 415,000 patients diagnosed in 2020.1 There were nearly 120,000 breast cancer deaths in China in 2020, representing approximately 18% of global breast cancer deaths.1 Approximately one in five cases of breast cancer are considered HER2-positive.2

Binghe Xu, MD, Professor and Director of the Department of Medical Oncology, Cancer Hospital and Institute Cancer Hospital, Chinese Academy of Medical Sciences, said: "This approval marks an important day for the breast cancer community in China as patients with HER2-positive metastatic breast cancer continue to need additional treatment options. Despite initial treatment, patients with HER2-positive metastatic breast cancer will often experience disease progression, demonstrating the importance of early systemic disease control and the potential for Enhertu to help eligible patients with metastatic breast cancer."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "This first approval of Enhertu in China represents a significant advance in the treatment of HER2-targetable tumours and provides the opportunity for patients with previously treated HER2-positive metastatic breast cancer to benefit from this important medicine as a second line therapy. The approval underscores our commitment to patients in China, where there has been an increased incidence rate of breast cancer, as we continue to explore the potential benefits of Enhertu earlier in the treatment of HER2-directed metastatic breast cancer and across HER2-targetable cancers."

Kiminori Nagao, Head of the Asia, South and Central America (ASCA) Business Unit, Daiichi Sankyo, said: "Enhertu is extending the time before disease progression or death and helping to redefine outcomes for patients with previously treated HER2-positive metastatic breast cancer, and now physicians in China will have this important medicine as an option for their patients. With this approval, Enhertu has the potential to become a new standard of care in China in the second-line setting for patients with HER2-positive metastatic breast cancer."

The safety profile of Enhertu in DESTINY-Breast03 was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer and was consistent with previous clinical trials with no new safety concerns identified. The most common adverse reactions were nausea (75.9%), fatigue (49.4%), vomiting (49.0%), neutropenia (42.8%) and alopecia (37.0%).

This approval follows the Breakthrough Therapy Designation and Priority Review granted to Enhertu by China’s NMPA in this type of breast cancer in 2022.

Financial considerations
Sales of Enhertu in China are recognised by AstraZeneca and will be recorded as product sales on the profit and loss statement. Further details on the financial arrangements were set out in the March 2019 announcement of the collaboration.

Notes

Breast cancer and HER2 expression
Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide.3 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.3 In China, breast cancer is the most common cancer in women, with more than 415,000 patients diagnosed in 2020.1 There were nearly 120,000 breast cancer deaths in China in 2020, representing approximately 18% of global breast cancer deaths.1 Approximately one in five cases of breast cancer are considered HER2-positive.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers.4 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.5

Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.6,7

DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival (PFS) based on blinded independent central review (BICR). Overall survival (OS) is a key secondary efficacy outcome measure. Other secondary efficacy endpoints include objective response rate (ORR), duration of response, PFS based on investigator assessment and safety. Primary results from DESTINY-Breast03 were published in The New England Journal of Medicine,8 with updated PFS and OS results published in The Lancet.9

DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.