ADC Drugs For HER2 Positive Breast Cancer

According to the latest data, breast cancer has overtaken lung cancer to become the most common cancer among women, and the death rate is the second highest among female tumors, seriously affecting the physical and mental health of women around the world. Patients with abnormal expression of human epidermal growth factor receptor (HER2) account for 15%-20% of all breast cancers, which is highly invasive and has poor prognosis.

Although more drug choices such as pertuzumab and lapatinib on the basis of trastuzumab significantly prolong the survival of patients and further improve the prognosis, many patients are not sensitive to treatment and relapse and drug resistance occur in a short time, and the efficacy of traditional HER2-targeted drugs for breast cancer patients with low HER2 expression is not optimistic.

Mechanism of action of ADC drugs

Antibody conjugate drugs (ADCs) are a type of novel antitumor drugs in continuous development. They combine the high specificity of monoclonal antibody drugs with the high activity of small molecule cytotoxic drugs, which can improve the targeting of antitumor drugs and reduce the probability of toxic and side effects.

An antibody drug conjugate (ADC) consists of three core elements: an antibody that targets a target antigen, a cytotoxic payload, and a linker that binds the two.

Potent cytotoxic drugs can be targeted to tumor cells with chemotherapeutic cytotoxic properties by means of selective monoclonal antibodies against specific or preferentially expressed antigens on target cells. Free cytotoxic agents can be used to create a more favorable therapeutic window for cytotoxic drugs, which not only reduces the concentration of peripheral toxic drugs, but also improves the efficiency and intensity of effective anti-tumor substances. Some ADCs show efficacy by targeting delivery payloads in breast cancers with low HER2 expression.

Of the 15 ADC drugs currently approved, three are used to treat breast cancer: Enhertu (T-DXd, DS-8201), Trodelvy (sacituzumab govitecan/SG, Goxaltuzumab) and ado-trastuzumab emtansine (T-DM1). Two are for HER2 breast cancer ADCs.

T-DM1(Ado-trastuzumab Emtansine)

T-DM1 is the first ADC drug to target HER2-positive breast cancer.

T-DM1, which is bound by trastuzumab and tubulin inhibitor DM1 via a stable, non-lytic, non-reducing thioether linker, was first approved by the FDA in 2013 for use in advanced breast cancer patients with HER2-positive metastases or who have been treated with trastuzumab and taxanes drugs.

Its approval was based on the EMILIA Phase III clinical study and the EMILIA Bridging Study in China, which showed that T-DM1 improved overall survival (OS) and progression-free survival (PFS), as well as better objective response rate (ORR) and median duration of response (DoR) compared to Lapatinib combined with capecitabine.

It will be listed in China in 2020, it has been approved for adjuvant therapy in HER2-positive early breast cancer patients with residual invasive lesions (non-pCR) after receiving taxane combined trastuzuab-based neoadjuvant therapy and for monotherapy in HER2-positive, unresectable locally advanced or metastatic breast cancer patients receiving taxane combined trastuzumab therapy.

Therefore, in the 2023 update of CSCO Guidelines for the Diagnosis and treatment of breast cancer, for patients with HER-2 positive breast cancer after neoadjuvant therapy, only trastuzumab was used in preoperative anti-HER-2 treatment, and non-pCR, T-DM1 evidence recommended for grade I was adjusted from 1B to 1A. For patients with HP and non-pCR in preoperative anti-HER-2 therapy, the evidence for T-DM1 recommended for grade I was adjusted from 1B to 2A. In addition, in the rescue treatment of advanced breast cancer with positive HER-2, the evidence level of "T-DM1" in trastuzumab treatment failure stratified patients was adjusted from 1B to 1A.

At present, there are also clinical trials on T-DM1 in CompassHER2 Rd test to evaluate whether the compasTI SHER2 test in combination with the tyrosine kinase inhibitor Tucatinib is better than T-DM1 alone. The HER2CLIMB-02 trial evaluated whether combination with Tucatinib was superior to T-DM1 monotherapy in patients previously receiving taxus + trastuzumab.

T-DXd, DS-8201 (Trastuzumab)

T-DXd (DS-8201) is an ADC that combines the anti-HER2 monoclonal antibody Trastuzumab with a topoisomerase Ⅰ inhibitor (Dxd) by means of an enzyme-cleavable tetrapeptidyl ligand.

Launched in the United States on December 21, 2019, the drug is the first official FDA approval of trastuzumab for the posterior treatment of HER2-positive breast cancer, based on stunning data from the DESTINY Breast01 study. Earlier this year, trastuzumab was approved domestically as a single drug for the treatment of unresectable or metastatic HER2-positive adults with breast cancer who have previously received one or more anti-HER2 drugs.

Up to now, trastuzumab has been approved in at least 5 tumor indications worldwide, including HER2-positive breast cancer, gastric cancer, gastroesophageal junction cancer, breast cancer with low HER2 expression, and non-small cell lung cancer.

Its domestic approval is based primarily on DESTINY Breast03, which has shown that trastuzumab (T-DXd), in contrast to Ado-trastuzumab Emtansine (T-DM1), is effective in treating HER2-positive unresectable and/or metastatic breast cancer in patients previously treated with trastuzumab and taxane. Reduced the risk of disease progression or death by 72% (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.22-0.37; p

Hunan Huateng Pharmaceutical Co. Ltd.
Address: Lugu Business Plaza E1, Yuelu District, Changsha City, Hunan Province, China
Manufacturing Base: Tongguan Kiln, Wangcheng district, Changsha, Hunan, China
Email: sales@huatengusa.com
Website: https://us.huatengsci.com
Zip code: 410205
Telephone: +86 731 89916275
Fax: +86 0731-82251112-818

Huateng Pharma is a leading and professional manufacturer which can provide pharmaceutical intermediates, PEG derivatives, biochemical reagents, APIs, Vitamin D Derivatives and so on. We have a 34,000 square meter manufacturing site with advanced design concept of intelligent manufacturing, which can realize the integration of the production process and accomplish the complete transformation of lab scale - pilot plant - large-scale commercial production, with an annual capacity of more than 1 billion RMB.

This release was published on openPR.