Androgen Drug to Be Tested for TNBC in Phase II Trial

A News Release from Medivation

Medivation, Inc.and Astellas Pharma Inc. today announced enrollment of the first patient in a global Phase 2 clinical trial evaluating enzalutamide as a single agent for the treatment of advanced, androgen receptor (AR)-positive, triple-negative breast cancer (TNBC). Medivation is conducting this study under its agreement with Astellas.

"The initiation of this Phase 2 study marks an important milestone as we expand our enzalutamide development program beyond prostate cancer to explore the clinical efficacy of enzalutamide in triple-negative breast cancer, where there is a significant unmet medical need," said David Hung, M.D., president and chief executive officer of Medivation, Inc. "We plan to present the results from the Phase 1 study in breast cancer at an upcoming scientific conference."

The Phase 2 open label, single-arm, multicenter trial plans to enroll approximately 80 patients with AR-positive, TNBC at sites in the United States, Canada and Europe. The primary endpoint of the trial is clinical benefit rate, defined as the proportion of patients with a best response of complete response, partial response or stable disease at ≥ 16 weeks. All patients will receive enzalutamide at a dose of 160 mg to be taken orally once daily. Information about patient eligibility and enrollment can be obtained by calling 800-888-7704 ext. 5473 or e-mailing clintrials.info@us.astellas.com.

TNBC is a type of cancer which does not express any of the three most commonly targeted receptors in breast cancer: estrogen, progesterone and HER2. TNBC remains an area of significant unmet medical need. Currently, there are no approved targeted therapies for these patients, who are typically treated with multiple regimens of chemotherapy. AR-positive breast cancer is a recently-identified subtype of TNBC that can express high levels of the androgen receptor.

Enzalutamide is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors, and inhibit androgen receptor nuclear translocation and interaction with DNA.

NOTE: XTANDI(R) (enzalutamide) capsules is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel. It can cause fetal harm and is contraindicated in women who are or may become pregnant.

Drugs to Block CD73 Successfully Target Chemo-Resistant TNBC

A news release from Centre hospitalier de l'Université de Montréal (edited by Pat to eliminate fearful language]:

MONTREAL, June 26, 2013 /CNW Telbec/ - An international research team of Canadian and Australian scientists have found that an enzyme in triple-negative breast cancer makes patients less responsive to chemotherapy. 

Triple negative breast cancer accounts for 15% of all breast cancers and is characterized by the absence of three key receptors (oestrogen receptor, progesterone receptor and the human epidermal growth factor receptor 2). Standard treatment, such as hormone therapy, cannot be used for triple negative breast cancer.

In a study published in the online version of the Proceedings of the National Academy of Sciences of the United States, the team found that CD73 made the breast cancer more resistant to chemotherapy with anthracyclines. This drug works not only by killing the tumour cells, but also by activating the body's anti-tumour immune response.

The research revealed that the overexpression of CD73 inhibits the body's immune response to cancer. Moreover, the heightened presence of CD73 is associated with a higher risk of distant metastases, the principal cause of death in breast cancer.

"These results are quite encouraging," says John Stagg, M.D,  assistant professor in the Faculty of Pharmacy at the University of Montreal and a researcher affiliated with Montreal Cancer Institute. "Because they suggest that therapies specifically designed to block the action of CD73 could make it possible to enhance the beneficial effects of anthracycline-based therapies." Indeed, in experiments with laboratory animals, Stagg's team showed that combining standard anthracycline treatment with anti-CD73 therapy prolonged survival by over 50%. More research is required to determine whether anti CD73 therapies can also be effective with other chemotherapeutic agents.

Human trials of inhibitors of CD73 could begin within five years, meaning that there is hope on the horizon for triple negative breast cancer patients.

Looking for a Clinical Trial for TNBC?

Are you looking for the TNBC clinical trial that most suits your needs and for which you are eligible?  A researcher at Harvard, Maytal Bivas-Benita, is currently designing a portal that patients can use in their search for trials, but she would like your help.

What challenges are you encountering on your search?  Maytal would love to talk with you, help you with your research, and use this to help others.  As she says, she would be your personal scientific consultant.

Here’s how she explains it:

My aim is to provide the patient with a basic understanding of the drug that is being tested, the possible mechanism of action, the relevance to TNBC, outcome in other indications (if available) and potential side effects (if previously identified). This information will give patients a better idea of what they are getting into. 

Different patients will have different considerations in selecting a trial (such as distance from home, reputation of the clinical site, potential benefits, potential toxicity, etc). It is up to each patient to make the right decision by carefully considering all their options. 

I am in the early stages of developing this approach and I would like to work together with patients who are looking for clinical trials. This will help me learn and understand the decision-making process. I am not a medical doctor, I am a scientist with a broad pharmaceutical background and extensive research experience. You can think of me as your personal (free) scientific consultant.

If you are interested in talking with Maytal, you can email her at maytalb@mac.com

Today's Goal

Worry less, appreciate more.