Estrogen Receptor Degrader Shows Promise in ER-Positive Breast Cancer

A new strategy in the treatment of estrogen receptor (ER) breast cancer may be in the form of an ER degrader. Like the antiestrogen tamoxifen (Soltamox, Nolvadex), this treatment also prevents estrogen from stimulating tumor growth.

In this proof-of-concept study, the ER-degrader GDC-0810 was deemed to be safe and tolerable in postmenopausal women with advanced ER-positive breast cancer. The treatment not only targets the ER, but also causes ER degradation, according to the preliminary data of this phase I/IIa clinical trial.

These results were presented at the American Association for Cancer Research (AACR) Annual Meeting, April 18-22, 2015 in Philadelphia.¹

GDC-0810 was given to 41 patients with advanced or metastatic ER-positive breast cancer patients in the phase I dose-escalation part of the clinical trials as a daily regimen. Testing for toxicity was evaluated from day 7 through the first cycle of treatment (35 days total). After assessing how patients tolerated the dose, they were assigned sequentially to escalating doses of the study drug. All patients were treated until disease progression, unacceptable toxicity, or patient withdrawal from the study.

The drug was given once or twice daily; some patients took it with food and others on an empty stomach. Most side effects were gastrointestinal; including diarrhea, nausea, fatigue, vomiting, flatulence, and decreased appetite. Additionally, some patients experienced anemia. Based on this data, the phase II dose was 600 mg of GDC-0810, taken once daily with food.

To measure the efficacy of the treatment, fluoroestradiol (FES) positron emission tomography (PET) was used, which correlates with ER expression and predicts response. The test showed that GDC-0810 occupied the ER at all doses of the antiestrogen, specifically in patients with estrogen receptor 1 (ESR1) mutations. This is important because ESR1 mutations can cause resistance to standard endocrine therapies.

Researchers have a continued interest in analyzing whether GDC-0810 can benefit patients with ESR1 gene mutations. This study is ongoing and still recruiting patients.²

References:

• American Association for Cancer Research. (2015). Investigational ER Degrader Safe, With Early Signs of Antitumor Activity Against Advanced ER-positive Breast Cancer.
• ClinicalTrials.gov. (2015). A Study of ARN-810 (GDC-0810) in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer.