Enzalutamide: Indication of major added benefit for over 75-year-olds

In continuation of my update on enzalutamide

According to the findings, in comparison with watchful waiting the drug can prolong overall survival and delay the occurrence of disease complications. In men aged 75 years or older, IQWiG sees an indication of a major added benefit. There is also an indication of an added benefit in younger men; however, the extent is rated as "considerable."

Approval study terminated prematurely

The assessment was based on a randomized controlled trial (PREVAIL), which was the approval study for the indication described above. In this study, patients received either enzalutamide or a placebo, while the hormone-blocking medication was continued in all patients. In each study arm, treatment was continued until either the disease worsened (progression) or safety concerns arose, for example, because toxicity was too high.

As the interim analysis planned for the outcome "overall survival" had already shown good efficacy of enzalutamide, this was considered as the final Analysis.

Survival advantage depends on age

The difference in overall survival is statistically significant between the two study arms. However, as the further analysis of the data shows, this advantage is age dependent. It is greater in older men (75 years or more) than in younger ones. In each case, the IQWiG researchers derive an indication of an added benefit from these results, albeit with a different extent (major or minor).

Bone-related complications occur later

The study data also showed relevant group differences in favour of enzalutamide for other outcomes. For instance, bone-related complications occurred later in patients receiving enzalutamide than in those receiving placebo. IQWiG sees an indication of an added benefit here.

In addition, it took longer until opiates were used, that is, severe pain occurred later in patients receiving enzalutamide. This also applies to the occurrence of side effects (severe and serious adverse events) and the discontinuation of treatment due to side effects. Health-related quality of life also deteriorated later.

Enzalutamide: Indication of major added benefit for over 75-year-olds  

Novel compound holds potential for next-generation prostate cancer treatment

In the search for new ways to attack recurrent prostate cancer, researchers at Duke Health report that a novel compound appears to have a unique way of blocking testosterone from fueling the tumors in mice.

The potential foundation for a next-generation therapy, called tetraaryl cyclobutane, or CB, is being studied as an option for prostate tumors that have grown resistant to current anti-androgen drugs, notably enzalutamide. (see below structure)

"Prostate cancer is the most prevalent form of cancer in men, and the principal driver of tumor growth is the androgen receptor," said John D. Norris, Ph.D., associate research professor in the Department of Pharmacology & Cancer Biology at Duke and senior author of a study published online Aug. 8 in the journal Nature Chemical Biology.

"Suppression of androgen receptor function by anti-endocrine therapies is initially effective, but most tumors develop resistance, resulting in a more aggressive cancer," Norris said. "Our research has been focused on finding a new approach to suppressing androgen receptor activity, because even in situations where tumors are resistant to current therapies, the androgen receptor remains a viable target."

  

Norris and colleagues focused on a group of CB compounds developed in collaboration with scientists at the University of Illinois at Urbana-Champaign. The compounds act as competitive inhibitors of androgen receptors, but are structurally different from current anti-androgens such as enzalutamide.

One of the CB compounds, in particular, inhibits mutant forms of the androgen receptors that promote resistance to enzalutamide. It functions by preventing the androgen receptor from entering the nucleus of the cell where it can promote tumor growth.

"It's encouraging that this compound has a different mechanism of action when compared to current therapies, which gives it a good chance of having efficacy in resistant disease," Norris said. "We have shown in animal models that the compound has activity against prostate tumors where enzalutamide fails."

Norris said additional studies are underway in additional animal models and in tests with other forms of cancer, including breast cancer.

Ref: http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.2131.html#compounds

Novel compound holds potential for next-generation prostate cancer treatment

FDA approves Enzalutamide (XTANDI Capsules)

Enzalutamide (marketed as Xtandi and formerly known as MDV3100) is an androgen receptor antagonist drug developed by the pharmaceutical company Medivation for the treatment of castration-resistant prostate cancer  currently in phase 3 clinical trials. Medivation has reported up to an 89% decrease in prostate specific antigen serum levels after a month of taking the medicine. Early preclinical studies also suggest that enzalutamide inhibits breast cancer cell growth. In August of 2012, the U.S. Food and Drug Administration approved enzalutamide (see structure) for the treatment of castration-resistant prostate cancer......

 
Approved Drugs > Enzalutamide (XTANDI Capsules)

Golden age of prostate cancer treatment hailed as fourth drug in two years extends life

We know that, Enzalutamide (formerly known as MDV3100, see the structure) is an experimental androgen receptor antagonist drug developed by the pharmaceutical company Medication for the treatment of castration-resistant prostate cancer currently in phase 3 clinical trials. Results so far have been encouraging; Medivation has reported up to an 89% decrease in prostate specific antigen serum levels after a month of taking the medicine. Early preclinical studies also suggest that enzalutamide inhibits breast cancer cell growth. 

Researchers from Institute of Cancer Research, London, and its partner hospital The Royal Marsden NHS Foundation Trust jointly led the new Phase III trial of enzalutamide and the Phase III trials of two other drugs, cabazitaxel and abiraterone. Abiraterone was also discovered at The Institute of Cancer Research and was recently made available on the NHS. A further drug sipuleucel-T has also been shown to extend life in the two-year period.

"What we're seeing now is an unprecedented period of success for prostate cancer research, with four new drugs shown to extend life in major clinical trials in just two years, and several others showing promise. It truly is a golden age for prostate cancer drug discovery and development" claims Prof. Martin Gore....

Golden age of prostate cancer treatment hailed as fourth drug in two years extends life

New Drug May Boost Survival for Advanced Prostate Cancer Patients: Study - Drugs.com MedNews

A pill that blocks male hormone activity can improve survival and delay the need for chemotherapy in men with advanced prostate cancer, a new clinical trial has found.

Men who took a daily dose of the drug enzalutamide started chemotherapy nearly a year and a half later than men who received a placebo, even though their prostate cancer had spread to other parts of their bodies, said senior study author Dr. Tomasz Beer, deputy director of the Knight Cancer Center at Oregon Health and Science University.

New Drug May Boost Survival for Advanced Prostate Cancer Patients: Study

Androgen receptors found to be a potential target in breast cancer

In continuation of my update on Enzalutamide

We know that, The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone  in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor...

Estrogen and progesterone receptors, and the gene HER2 - these are the big three markers and/or targets in breast cancer. Evidence presented at the AACR Annual Meeting 2013 adds a fourth: androgen receptors.

"This is a continuing line of work with all evidence pointing toward the addition of the androgen receptor as potential target and useful marker in all of the major subtypes of breast cancer," says Jennifer Richer, PhD, investigator at the University of Colorado Cancer Center and co-director of the CU Cancer Center Tissue Processing and Procurement Core.

 The finding of androgen receptors (AR) as a potential target in breast cancer is especially important in light of its prevalence in breast cancers that don't express other hormone receptor targets or have developed resistance to treatments that target estrogen dependence. Overall, approximately 77 percent of breast cancers are positive for AR, including 88 percent of cancers that are estrogen receptor positive, 59 percent of those that are HER2 positive, and 20-32 percent of triple negative breast cancers.....

Androgen receptors found to be a potential target in breast cancer