April 22, 2024

Medical Trend

Medical News and Medical Resources

Treating Breast Cancer with “Androgen Receptor”

Treating Breast Cancer with “Androgen Receptor”: Endocrine Therapy Resistant Patients Also Benefit!



Treating Breast Cancer with “Androgen Receptor”: Endocrine Therapy Resistant Patients Also Benefit!

Breast cancer is one of the most common malignancies in women worldwide, and its development is closely related to sex hormones and their receptors. Androgen receptor (AR) is a type of steroid hormone receptor that is highly expressed in breast cancer. Recent studies have suggested that the AR pathway interacts with estrogen receptor (ER), human epidermal growth factor receptor-2 (HER2), and several other signaling pathways, with AR acting as a tumor suppressor in ER-positive breast cancer.

Selective AR modulators (SARMs) bind highly specifically to AR and exert their effects in a tissue-selective manner, avoiding adverse reactions such as menstrual disorders, decreased libido, and hirsutism. Enobosarm is an oral, nonsteroidal SARM of the arylpropionamide class. Previous studies have shown that enobosarm can provide significant anti-tumor activity in ER-positive metastatic breast cancer patients who have undergone multiple lines of treatment.

Recently, The Lancet Oncology published the results of a Phase 2 trial of enobosarm in patients with advanced breast cancer. The analysis showed that ER-positive, AR-positive, HER2-negative advanced breast cancer patients who had received conventional endocrine therapy could also benefit from enobosarm treatment. Additionally, the proportion of patients who clinically benefited from enobosarm treatment was similar for both the 9 mg and 18 mg daily doses.

Treating Breast Cancer with "Androgen Receptor": Endocrine Therapy Resistant Patients Also Benefit!

This randomized, open-label, multicenter, multinational, parallel-design Phase 2 trial evaluated the efficacy and safety of two different doses of enobosarm in ER-positive, AR-positive, HER2-negative advanced breast cancer patients. Patients were randomized in a 1:1 ratio to receive either 9 mg or 18 mg of enobosarm orally once daily. The primary endpoint of the study was the clinical benefit rate at week 24 in AR-positive patients (who constituted the evaluable population).

From September 10, 2015, to November 28, 2017, a total of 136 patients were enrolled (72 in the 9 mg group; 64 in the 18 mg group). Of these, 102 patients (75%) constituted the evaluable population (50 in the 9 mg group; 52 in the 18 mg group), with a median age of 60.5 years in the 9 mg group and 62.5 years in the 18 mg group. The most common sites of breast cancer metastasis in these patients were the bone, liver, lungs, and lymph nodes. Additionally, these patients had previously received second-line endocrine therapy (including adjuvant, neoadjuvant, or advanced endocrine therapy).

The median follow-up time for the patients was 7.5 months. At week 24, 32% of patients in the 9 mg group and 29% in the 18 mg group achieved clinical benefit, with 4 patients (12%) in the 9 mg group and 2 patients (5%) in the 18 mg group achieving partial or complete responses. Furthermore, the median progression-free survival (PFS) was 5.6 months in the 9 mg group and 4.2 months in the 18 mg group.

In terms of safety, 8% of patients in the 9 mg group and 16% in the 18 mg group experienced Grade 3 or 4 drug-related adverse events, with the most common being elevated liver transaminases (4% in the 9 mg group; 3% in the 18 mg group), hypercalcemia (3% in both groups), and fatigue (1% in the 9 mg group; 3% in the 18 mg group).

In conclusion, enobosarm demonstrates significant anti-tumor activity in ER-positive, HER2-negative advanced breast cancer patients. This suggests that activating AR can provide clinical benefits for these patients, and future clinical researchers should further explore selective AR activation strategies for the treatment of AR-positive, ER-positive, HER2-negative advanced breast cancer. The paper emphasizes that this study is the “first published study using SARM to activate AR for the treatment of advanced breast cancer.”

Treating Breast Cancer with “Androgen Receptor”: Endocrine Therapy Resistant Patients Also Benefit!


Reference:

1.Current Status and Perspectives of Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Hematological Malignancies. Cancers (Basel).2022 Jul; 14(13): 3230.

(source:internet, reference only)

Disclaimer of medicaltrend.org


Important Note: The information provided is for informational purposes only and should not be considered as medical advice.