Bayer and Orion Initiate Phase III Trial of Novel Prostate Cancer Agent ODM-201 in Men with High-Risk Non-Metastatic Castration-Resistant Prostate Cancer

The gist: A new clinical trial—a research study with volunteer patients—is testing a new prostate cancer drug. The drug is called ODM-201 and is being given to participating patients in Finland. Specifically, the drug is being tested in”men with castration-resistant prostate cancer (CRPC) who have rising Prostate-Specific Antigen (PSA) levels and no detectable metastases.”

“Bayer HealthCare and Orion Corporation, a pharmaceutical company based in Espoo, Finland, have begun to enroll patients in a Phase III trial with ODM-201, an investigational novel oral androgen receptor (AR) inhibitor in clinical development for the treatment of patients with prostate cancer. The study, called ARAMIS, evaluates ODM-201 in men with castration-resistant prostate cancer (CRPC) who have rising Prostate-Specific Antigen (PSA) levels and no detectable metastases. The trial is designed to determine the effects of the treatment on metastasis-free survival (MFS).

“ ‘The field of treatment options for prostate cancer patients is evolving rapidly. However, once prostate cancer becomes resistant to conventional anti-hormonal therapy, many patients will eventually develop metastatic disease,’ said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. ‘The initiation of a Phase III clinical trial for ODM-201 marks the starting point for a potential new treatment option for patients whose cancer has not yet spread and is an important milestone for Bayer in our ongoing effort to meet the unmet needs of people affected by cancer.’ ”

UPDATE 1-U.S. FDA Approves Expanded Use of Medivation Prostate Cancer Drug

The gist: When a drug company creates a new cancer treatment, the treatment must be approved by the U.S. Food and Drug Administration (FDA) before doctors in the U.S. can prescribe it. An FDA approval for a new drug usually specifies the particular kinds of patients who are allowed to be treated. In 2012, drug called Xtandi was FDA-approved for treating people with metastatic castration-resistant prostate cancer (mCRPC) who have been previously but unsuccessfully treated with chemotherapy. Now, the FDA has also approved Xtandi for people with mCRPC who have not yet tried chemotherapy.

“U.S. health regulators approved the use of Medivation Inc’s and Astellas Pharma Inc’s advanced prostate cancer drug Xtandi in men who have not yet received chemotherapy, the companies said on Wednesday, significantly expanding the potential patient population for the oral medicine.

“The expanded Food and Drug Administration approval will also enable the drug to better compete with Johnson & Johnson’s Zytiga. The approval triggers $90 million in milestone payments to Medivation by Japan’s Astellas under a collaboration agreement.

“Xtandi, known chemically as enzalutamide, originally gained U.S. approval in 2012 for use in patients with castration-resistant prostate cancer that has spread beyond the prostate only after they had first received chemotherapy treatment.

” ‘The average duration of treatment should double and the addressable patient population triple in the pre-chemo setting,’ Sanford Bernstein analyst Geoffrey Porges said in a research note earlier this week.”

ADT Heads List of Therapies in New Prostate Ca Guide

Editor’s note: The American American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) have jointly published a new guideline for treating metastatic castration-resistant prostate cancer (mCRPC). The guideline says that androgen deprivation therapy (ADT) should be the foundation of treatment, and should be given along with certain drugs. The guideline specifies which kinds of patients should receive which drugs, in addition to ADT.

“Indefinite continuation of androgen deprivation therapy (ADT) remains the cornerstone of systemic treatment for metastatic castration-resistant prostate cancer (mCRPC), augmented by new agents, according to a joint guideline from American and Canadian oncology groups.

“In addition to ADT (medical or surgical), clinicians should offer patients with mCRPC abiraterone (Zytiga) plus prednisone, enzalutamide (Xtandi), and radium-223 (Xofigo), all of which have favorable benefit-harm profiles, the guideline indicated. Patients also may be offered docetaxel plus prednisone, but should be thoroughly informed of potential toxicity.

“Other systemic agents have niche roles in the treatment of mCRPC, as recommended by the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO). The guideline was published online in the Journal of Clinical Oncology and is available on the ASCO website.”

Enzalutamide Improved Health-Related Quality of Life in Prostate Cancer

Editor’s note: This article discusses the results of a clinical trial—a research study with volunteer patients. All patients who participated in the trial had metastatic castration-resistant prostate cancer that had worsened during treatment with the chemotherapy drug docetaxel. The study found that treatment with the drug enzalutamide reduced symptoms and improved quality of life for the patients.

“Enzalutamide was associated with significant improvements in disease-related symptoms and all aspects of health-related quality of life among men with metastatic castration-resistant prostate cancer, according to results of the phase 3, double blind AFFIRM trial.

“The trial included 1,199 patients who progressed during treatment with docetaxel.

Karim Fizazi, MD, PhD, medical oncologist in the department of cancer medicine at Institut Gustave Roussy at the University of Paris, and colleagues randomly assigned 800 patients to 160 mg daily enzalutamide (Xtandi; Astellas, Medivation). The other 399 patients received placebo.”

Investigational Prostate Cancer Drug Decreased PSA Levels with Low Toxicity

The gist: Researchers conducted a clinical trial with volunteer patients to test a new drug for nonmetastatic castration-resistant prostate cancer. Patients participating in the trial were treated with the drug orteronel. It was found that orteronel decreased PSA levels (high PSA levels may correlate with worsening disease).

“Monotherapy with the investigational agent orteronel decreased PSA levels in patients with nonmetastatic castration-resistant prostate cancer, according to results of a phase 2 study.

“Toxicities were moderate and manageable, and administration of the drug without steroids appeared to be feasible, Maha Hussain, MD, FACP, professor of medicine and urology at the University of Michigan Comprehensive Cancer Center, and colleagues wrote.”

New Androgen Receptor Inhibitor Shows Activity in Metastatic Castration-Resistant Prostate Cancer

The gist: Some patients have what is known as metastatic “castration-resistant” prostate cancer (mCRPC)—metastatic cancer that worsens despite treatment with traditional hormone therapy. Researchers are hard at work to discover solutions for these treatment-resistant cancers. A recent clinical trial with volunteer mCRPC patients tested a new treatment called ODM-201. The treatment appeared to be safe, and men who took it had promising decreases in their PSA levels. Further testing is needed to see how effective ODM-201 might be in treating mCRPC.

“ODM-201 is a novel androgen receptor inhibitor—structurally distinct from enzalutamide (Xtandi)—that acts via high-affinity binding to the androgen receptor and inhibition of receptor nuclear translocation. In the phase I/II ARADES trial reported in The Lancet Oncology, Fizazi et al identified no maximum tolerated dose and observed prostate-specific antigen (PSA) responses in men with progressive metastatic castration-resistant prostate cancer…

“In this study, conducted in 23 U.S. and European hospitals, no dose-limiting toxicity or maximum tolerated dose was found at an oral ODM-201 dose range of 200 mg to 1,800 mg daily in the phase I portion.  In the phase II portion, 110 patients were randomly assigned to receive doses of 200 mg (n =38), 400 mg (n = 37), or 1,400 mg (n = 35); four, seven, and three patients treated at these dose levels in the phase I portion were also advanced to phase II evaluation. The primary endpoint was ≥ 50% reduction in serum PSA at week 12…

“Among evaluable patients, PSA response at 12 weeks was observed in 29% at 200 mg, 33% at 400 mg, and 33% at 1,400 mg. Response rates were higher among patients who were chemotherapy-naive and had not received CYP17 inhibitor treatment (50%, 69%, and 86%). Follow-up is ongoing.”

ASCO 2014 — Takeaways for Prostate Cancer Patients

Every year, thousands of people gather for the American Society of Clinical Oncology (ASCO) Annual Meeting. This year’s meeting took place in Chicago, Illinois. Here are some of the most notable new developments in prostate cancer treatment presented at ASCO 2014: Continue reading…

Takeda Announces Termination of Orteronel (TAK-700) Development for Prostate Cancer in Japan, U.S.A. and Europe

“Takeda Pharmaceutical Company Limited announced today that it has voluntarily decided to end the development program for orteronel (TAK-700) for prostate cancer. The decision follows the results of two Phase 3 clinical trials in metastatic, castration resistant prostate cancer (mCRPC). The studies found while orteronel plus prednisone could extend the time patients lived before their cancer progressed, it did not extend overall survival in these patients. After careful consideration of the data from these trials, the company has determined that the drug has not demonstrated a clinical profile sufficient to move forward in mCRPC, given the availability of other therapies.”

Editor’s note: Orteronel is a drug that showed some promise in for treating metastatic castration-resistant prostate cancer (mCRPC). However, the manufacturers of the drug found that it was not good enough compared to other treatments, and they have decided to stop developing it. We recently posted a news story in which orteronel showed mixed results as a treatment for mCRPC.

Early Trial of Cabozantinib and Abiraterone Shows Promise in Prostate Cancer

“A phase I trial that combined the investigational therapy cabozantinib with the already approved abiraterone acetate in metastatic castration-resistant prostate cancer (CRPC) patients shows that the two agents are tolerable, with the potential for improved efficacy.

“Christopher Sweeney, MBBS, medical oncologist at Dana-Farber Cancer Institute in Boston, presented the results (abstract #5027) at the American Society of Clinical Oncology Annual Meeting, held May 30–June 3 in Chicago.”

Editor’s note: A clinical trial to test a new treatment on volunteer patients found that a combination of the drugs cabozantinib and abiraterone acetate may be beneficial for treating metastatic castration-resistant prostate cancer (CRPC), but further testing is needed.