Drugs Home in on Bone Metastases in Prostate Cancer

Bone metastases are common in patients with metastatic castration-resistant prostate cancer (CRPC). They are associated with increased risk of death due to a number of complications such as bone fractures, compression of the spinal cord, and pain. Radiation of the affected bone sites is used as a palliative measure to relieve pain. The U.S. Food and Drug Administration (FDA) has also approved certain drugs for treatment of bone metastases in CRPC including the following: Continue reading…

Medivation and Astellas Announce Phase 3 Study of Enzalutamide In Men With High-Risk, Hormone-Sensitive, Non-Metastatic Prostate Cancer That Has Recurred Following Definitive Local Therapy

The gist: Two drug companies are partnering to figure out how to treat patients who already had radical prostatectomy and/or radiation therapy to treat their high-risk, hormone-sensitive, non-metastatic prostate cancer, but who then experienced rising PSA levels. The companies will use a clinical trial with volunteer patients to test whether the drug enzalutamide might help. If you are a patient interested in participating in the trial, find out more at clinicaltrials.gov.

“Medivation Inc. (NASDAQ: MDVN) and Astellas today announced plans to initiate a global Phase 3 clinical trial that will evaluate the efficacy and safety of enzalutamide in patients with high-risk, hormone-sensitive, non-metastatic prostate cancer that has biochemically recurred (rising prostate-specific antigen [PSA] level) following definitive local therapy with radical prostatectomy and/or radiation therapy. Currently, there is no prescription medicine specifically approved in the United States for these patients.

“ ‘It is estimated that approximately one third of men in the United States experience a rising PSA, also known as biochemical recurrence, after localized therapy for the treatment of prostate cancer,’ said Lynn Seely, M.D., chief medical officer of Medivation, Inc.  ‘This trial will determine if enzalutamide can delay the development of metastatic prostate cancer in high-risk men with a rapidly rising PSA.  The initiation of this trial in collaboration with our partner Astellas showcases our mutual commitment to continue exploring the potential of enzalutamide in areas of significant unmet medical need.’ ”

“ ‘Following enzalutamide’s continued positive impact on overall survival and progression-free survival versus placebo in metastatic castration-resistant prostate cancer, we are looking forward to continuing to explore the medicine’s potential impact on patients at earlier stages of the disease,’ said Sef Kurstjens, M.D., Ph.D., chief medical officer of Astellas Pharma Inc. and president of Astellas Pharma Global Development, Inc.”

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.”

Blood Test for 'Nicked' Protein Predicts Prostate Cancer Treatment Response

“Prostate cancer patients whose tumors contain a shortened protein called AR-V7, which can be detected in the blood, are less likely to respond to two widely used drugs for metastatic prostate cancer, according to results of a study led by researchers at the Johns Hopkins Kimmel Cancer Center. If large-scale studies validate the findings, the investigators say men with detectable blood levels of AR-V7 should avoid these two drugs and instead take other medicines to treat their prostate cancer. A report on the work is described online Sept. 3 in the New England Journal of Medicine.

“The study evaluated two groups of 31 men with prostate cancer that had spread and whose blood levels of prostate-specific antigen (PSA) were still rising despite low testosterone levels. Investigators gave each man either enzalutamide (Xtandi) or abiraterone (Zytiga) and tracked whether their PSA levels continued to rise, an indication that the drugs were not working. In the enzalutamide group, none of 12 patients whose blood samples tested positive for AR-V7 responded to the drug, compared with 10 responders among 19 men who had no AR-V7 detected. In the abiraterone group, none of six AR-V7-positive patients responded, compared with 17 responders among 25 patients lacking AR-V7.

“Enzalutamide and abiraterone have been very successful in lengthening the lives of about 80 percent of patients with metastatic prostate cancer, says Emmanuel Antonarakis, M.D., assistant professor of oncology at Johns Hopkins, but the drugs do not work in the remaining 20 percent of patients.

” ‘Until now, we haven’t been able to predict which patients will not respond to these therapies. If our results are confirmed by other researchers, a blood test could use AR-V7 as a biomarker to predict enzalutamide and abiraterone resistance, and let us direct patients who test positive for AR-V7 toward other types of therapy sooner, saving time and money while avoiding futile therapy,’ says Antonarakis.”

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.”

Cancer Drugs Yervoy, Xtandi Get NICE Thumbs Up

“Cost regulators for the National Health Service in England and Wales have this morning issued guidance recommending the use of Bristol-Myers Squibb’s Yervoy (ipilimumab) for skin cancer and Astellas’ Xtandi (enzalutamide) for prostate cancer.

“First-line use of Yervoy will be funded in patients with advanced malignant melanoma when the full tumour cannot be removed or the cancer has spread to other parts of the body.

“The drug costs £3,750 per 10-ml vial or £15,000 per 40-ml vial, but B-MS has also agreed a patient access scheme with the Department of Health, in which it will be sold to the NHS at a discounted price.

“NICE analysis concluded that the most plausible cost per Quality Adjusted Life Year (QALY) was £47,900 for Yervoy compared with the chemotherapy dacarbazine and £28,600 per QALY compared with Roche’s Zelboraf (vemuraf [sic]).”

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…