December 8, 2021

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How about HER2-positive breast cancer resistance? 

How about HER2-positive breast cancer resistance?


How about HER2-positive breast cancer resistance?  US FDA announced that it has granted ARX788 fast track designation as a single-drug therapy for the treatment of advanced or metastatic HER2-positive breast cancer patients who have received one or more anti-HER2 therapies.


Recently, the US FDA announced that it has granted ARX788 fast track designation as a single-drug therapy for the treatment of advanced or metastatic HER2-positive breast cancer patients who have received one or more anti-HER2 therapies.

 

▌HER2-positive breast cancer treatment strategy

Human epidermal growth factor receptor 2 (HER2) positive accounts for about 20% of all breast cancers. This type of breast cancer is highly invasive and has a poor prognosis.

According to good doctors, trastuzumab, pertuzumab, lapatinib, lenatinib and other drugs are often used clinically, which brings more treatment options to breast cancer patients and significantly improves patients Prognosis. However, there are still some patients who do not respond to HER2 targeted drugs, or develop resistance after treatment for a period of time, and there are unfinished medical needs.

At the beginning of last year, Hercelium (Enmetrastuzumab, T-DM1) was approved for marketing in China! Indications: Survival after receiving neoadjuvant therapy based on taxanes combined with trastuzumab Adjuvant treatment of HER2-positive early breast cancer patients with aggressive lesions. This is the first antibody-conjugated drug (ADC) approved in China. Among them, trastuzumab is the antibody part, and Enmei is the additional chemotherapeutic part.

How about HER2-positive breast cancer resistance?  

T-DM1 was first approved by the FDA in May 2019 and has become the current international standard drug for the treatment of HER2-positive breast cancer. In addition, among ADC drugs, there are ARX788, Enhertu, etc. They provide more treatment options for patients with HER2-positive breast cancer.

 

▌Antibody conjugate drug: ARX788

ARX788 is a highly stable antibody-drug conjugate (ADC) targeting the HER2 receptor. It consists of two cytotoxic payload sites specifically coupled to an antibody with trastuzumab as the basic backbone.

By optimizing the number, location and chemical bonds of the cytotoxin AS269 payload and antibody binding, ARX788 is designed to maximize its activity in preclinical experiments. AS269 is a proprietary tubulin inhibitor specifically designed to form highly stable covalent bonds with synthetic amino acids.

A clinical trial on ARX788 evaluated its preliminary efficacy, safety, tolerability and clinical pharmacology data.

At present, relevant clinical trials have also been initiated in China. One of the results of the trial showed that the clinical disease control rate of phase 1 is 100%, and Enhertu is still effective after drug resistance. Moreover, ARX788 has a good drug effect and can have effects on other HER2-positive tumors, including gastric cancer, gallbladder cancer or cholangiocarcinoma.

This is an important milestone for ARX788, bringing innovative treatment options to patients with HER2-positive breast cancer.

 

▌Another “ADC star”: Enhertu

How about HER2-positive breast cancer resistance? 

In December 2019, the US FDA approved Enhertu (DS-8201) for the treatment of adult patients with HER2-positive metastatic breast cancer who have received 2 or more anti-HER2 drugs in metastatic disease.

Among the HER2-positive breast cancer patients who were resistant to Herceptin and T-DM1 treatment, Enhertu achieved an effective rate of 61.4%, demonstrating its strong ability to save the back line. For people with low HER2 expression, Enhertu is equally effective, yielding an effective rate of 37%.

The latest results of the subgroup of patients with breast cancer brain metastases announced at the ESMO conference in 2020 showed that the effective rate of Enhertu treatment group was 58.3%, the disease control rate was 91.7%, and the median PFS was 18.1 months. Reflects its efficacy in patients with brain metastases. Unfortunately, the drug is not currently on the market in China.

Patients with HER2-positive breast cancer are still facing the problem of drug resistance in clinical treatment, but as more and more new drugs and good drugs come out, the patient’s “ammunition library” is becoming more and more sufficient. HER2-positive breast cancer has become a chronic disease.

 

(source:chinanet, reference only)


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