Enhertu® Approved in China as the First HER2-Targeted Therapy for HER2-Low Metastatic Breast Cancer

ShanghaiJuly 12, 2023/PR Newswire/ -- Enhertu, an antibody-drug conjugate (ADC) jointly developed by Daiichi Sankyo and AstraZeneca^®（ENHERTU^®Trastuzumab deruxtecan for injection has been approved by the China National Medical Products Administration (NMPA) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received at least one prior systemic therapy in the metastatic setting, or who relapsed within 6 months after adjuvant chemotherapy or during adjuvant chemotherapy.

Enhertu^®It is a HER2-targeted antibody-drug conjugate jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

In China, breast cancer is the most common malignant tumor in women. According to statistics, there were 415,000 new cases of breast cancer in China in 2020.^[1], nearly 120,000 patients died, accounting for 18% of global breast cancer deaths.^[2]Among them, about half of the patients are considered to have low HER2 expression.^[3],[4],[5]。

This approval is based on the results of the Phase III clinical trial DESTINY-Breast04. The trial results were first presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. Prior to this approval, China's National Medical Products Administration had approved Enhertu in February 2023.^®Indicated 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.

According to the results of the DESTINY-Breast04 study, compared with chemotherapy, Enhertu^®The treatment group reduced the risk of disease progression or death by 50% (Hazard Ratio [HR]=0.50; 95% Confidence Interval [CI]: 0.40-0.63; p<0.0001) in patients with HR-positive and HR-negative HER2-low breast cancer. As assessed by Blinded Independent Central Review (BICR), Enhertu^®The median progression-free survival (PFS) in the treatment group was 9.9 months (95% CI: 9.0-11.3), compared to only 5.1 months (95% CI: 4.2-6.8) in the chemotherapy group, with a 36% reduction in the risk of death (HR=0.64; 95% CI: 0.49-0.84; p=0.001) for those receiving Enhertu.^®The median overall survival (OS) for treated patients was 23.4 months (95% CI: 20.0-24.8), compared to 16.8 months in the chemotherapy group.

Academician of the Chinese Academy of Engineering, Member of the Division of the Chinese Academy of Medical Sciences, National Cancer Center/Clinical Trial Research Center of Cancer Hospital, Chinese Academy of Medical Sciences (GCP）Director Professor Xu Binghe stated:"Approximately half of breast cancer patients have HER2-low expression, which is a relatively novel area in current breast cancer diagnosis and treatment. Therefore, providing personalized anti-HER2 therapy for these patients is of great significance in reshaping the landscape of breast cancer treatment. The approval of the ADC drug trastuzumab deruxtecan for injection in China marks the end of the era of binary classification into HER2-positive and HER2-negative, offering an entirely new treatment option for patients with HER2-low breast cancer. We are highly anticipating that this innovative drug will benefit more breast cancer patients in China."

Mr. Kiminori Nagao, Head of Daiichi Sankyo's Asia and Central/South America regions, stated:Following the HER2-positive indication, this time Enhertu^®Approval of the HER2-low indication marks the first time that patients with HER2-low expression have the opportunity to receive precise anti-HER2 treatment, bringing a new treatment option for patients with HER2-low metastatic breast cancer. Enhertu^® Is expected to become a new standard treatment option for Chinese patients with HER2-positive and low-expression metastatic breast cancer.

AboutDESTINY-Breast 04Research

DESTINY-Breast04 is a global, randomized, open-label, registrational Phase III trial evaluating Enhertu^®(5.4 mg/kg) versus physician's choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel) in patients with unresectable and/or metastatic HR-positive or HR-negative, HER2-low breast cancer who have received one or two prior chemotherapy regimens. Patients were randomized 2:1 to receive Enhertu.^®Or chemotherapy.

The primary endpoint of DESTINY-Breast04 is PFS in HR-positive patients based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomized patients (regardless of HR status), OS in HR-positive patients, and OS in all randomized patients (regardless of HR status). Other secondary endpoints include PFS based on investigator assessment, duration of response based on BICR and investigator assessment, and safety. DESTINY-Breast04 enrolled approximately 557 patients across multiple centers in Asia, Europe, and North America. For more information about the trial, please visitClinicalTrials.gov 。

About Breast Cancer andHER2Expression

Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths globally.^[6]Globally, there were over 2 million breast cancer patients in 2020, with nearly 685,000 deaths.^[7]In China, breast cancer is the most common cancer among women, with nearly 420,000 confirmed cases in 2020.^[8]In 2020, the number of breast cancer deaths in China was close to 120,000, accounting for about 18% of global breast cancer deaths.^[9]。

HER2 is a tyrosine kinase receptor pro-growth protein and one of many biomarkers expressed in breast cancer tumors.^[10]。

HER2 expression is determined through immunohistochemistry (IHC) and/or in situ hybridization (ISH) testing, with IHC estimating the number of HER2 proteins on cancer cells and ISH calculating the copy number of the HER2 gene in cancer cells.^[11],[12]HER2 testing can provide IHC and ISH scores for the entire HER2, and HER2 testing is now routinely used in metastatic breast cancer to determine the appropriate treatment strategy.^[13]In the past, HER2-positive cancer referred to HER2 expression levels of IHC 3+ or IHC 2+/ISH+, while HER2-negative cancer referred to HER2 expression levels of IHC 0, IHC 1+, or IHC 2+/ISH-.^[14]However, among all breast cancers, approximately half are HER2-low breast cancers (IHC 1+ or IHC 2+/ISH-).^{[15],[16],[17]}HER2 low expression can occur in both HR-positive and HR-negative breast cancer.^[18]。

Disclaimer: The usage of the investigational drug mentioned in this article has not been approved for the indication in China, and Daiichi Sankyo does not recommend any use of unapproved drugs.

References 

^[1] Wei Cao, et al. Chin Med J (Engl). 2021; 134(7): 783–91.

^[2] Wei Cao, et al. Chin Med J (Engl). 2021; 134(7): 783–91.

^[3] Schalper K, et al. Arch Pathol Lab Med. 2014;138:213-219.

^[4] Schettini F, et al. NPJ Breast Cancer. 2021;7:1.

^[5] Denkert C, et al. Lancet Oncol. 2021;22:1151-61.

^[6] Sung H, et al. CA Cancer J Clin. 2021;10.3322/caac.21660.

^[7] Sung H, et al. CA Cancer J Clin. 2021;10.3322/caac.21660.

^[8] Wei Cao, et al. Chin Med J (Engl). 2021; 134(7): 783–91.

^[9] Wei Cao, et al. Chin Med J (Engl). 2021; 134(7): 783–91.

^[10] Iqbal N, et al. Mol Biol Int. 2014;852748.

^[11] Iqbal N, et al. Mol Biol Int. 2014;852748.

^[12] Wolff A, et al. Arch Pathol Lab Med. 2018;142(11):1364–1382.

^[13] Iqbal N, et al. Mol Biol Int. 2014;852748.

^[14] Iqbal N, et al. Mol Biol Int. 2014;852748.

^[15] Schalper K, et al. Arch Pathol Lab Med. 2014;138:213-219.

^[16] Schettini F, et al. NPJ Breast Cancer. 2021;7:1.

^[17] Denkert C, et al. Lancet Oncol. 2021;22:1151-61.

^[18] Miglietta F, et al. NPJ Breast Cancer. 2021;7:137.