December 8, 2021

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New generation of oral SERD: Elacestrant as breast cancer endocrine therapy

New generation of oral SERD: Elacestrant as breast cancer endocrine therapy



 

New generation of oral SERD: Elacestrant as breast cancer endocrine therapy.  Fulvestrant can only be used in breast cancer endocrine therapy? Take a look at the new generation of oral therapy.

 

Breast cancer has become the world’s largest cancer, and how to better treat it has become a major problem.

The latest data from the World Health Organization show that breast cancer has surpassed lung cancer as the most common cancer in the world, and one in eight newly diagnosed cancer patients is breast cancer.

 

In all breast cancers, hormone receptor (ER/PR) positive accounts for about 80%, and the proliferation of such breast cancer cells is very dependent on hormone receptors. For this type of breast cancer patients, endocrine therapy is an effective treatment method.

 

However, the existing endocrine drugs have some problems, for example, they cannot completely inhibit ER signal transduction, and it is difficult to effectively inhibit the proliferation of cancer cells; the intramuscular injection formulation also limits its clinical application to a certain extent. Patients with ER-positive breast cancer urgently need new treatment options.

 

A novel selective estrogen receptor degrading agent (SERD) that can be administered orally, adds a new weapon to the “magazine” of patients with ER-positive breast cancer.

 

SERD is a small molecule drug that binds to the ER on the surface of cancer cells to reduce its stability and induce it to be degraded by the normal protein degradation mechanism of the cell, thereby reducing the level of ER and inhibiting the growth of cancer cells.

Unlike regulators that inhibit ER activity, SERD can more comprehensively inhibit its function by mediating ER degradation, and is expected to improve drug resistance caused by ER mutations.

 

Fulvestrant is the first SERD drug approved, but it requires injection, which limits the scope of application to a certain extent. The new generation of oral SERD is expected to change this dilemma and bring new treatment options for patients with ER-positive breast cancer.

 

Not long ago, the Journal of Clinical Oncology of the American Society of Clinical Oncology published a phase I clinical study led by Dr. Aditya Bardia, an oncologist at the Massachusetts General Hospital of Harvard Medical School. The effectiveness and safety of patients with negative advanced breast cancer.

 

 

▌A new generation of oral SERD: Elacestrant

Elacestrant is a new generation of selective estrogen receptor degrading agent, administered orally once a day.

New generation of oral SERD: Elacestrant as breast cancer endocrine therapy

 

This study included 57 patients with ER-positive, HER2-negative, postmenopausal metastatic breast cancer who failed multi-line treatment from 11 hospitals in the United States.

 

The results of the study show that: for such patients, the safety of oral Elacestrant (400 mg) once a day is tolerable (no dose-limiting toxic reactions occurred, and most adverse events are grade 1 to 2), and the single agent has anti-cancer activity And achieve partial relief.

 

The objective response rate of Elacestrant was 19.4%, 15% in patients who had previously received SERD treatment (52%), 16.7% in patients who had received CDK4/6i treatment (52%), and ESR1 mutations (50%) ) Among patients, it was 33.3%.

 

The overall clinical benefit rate (24 weeks) of Elacestrant was 42.6%, 56.5% in patients with ESR1 mutations, and 30.4% in patients who had previously received CDK4/6i treatment.

 

In addition, a phase III clinical trial comparing the efficacy of Elacestrant with standard endocrine therapy is underway and is worth looking forward to.

 

Experts remind: a new generation of oral SERD is of great significance to patients with metastatic ER-positive breast cancer, especially those who are resistant to endocrine therapy.

At present, in addition to Elacestrant, there are several oral SERDs under development, including: Giredestrant (GDC-9545), SAR439859, AZD9833.

Looking forward to more new therapies coming out, bringing new treatment options for this type of breast cancer patients.

 

 

 

 

New generation of oral SERD: Elacestrant as breast cancer endocrine therapy

(source:internet, reference only)


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