Radium-223 Dichloride Effective in CRPC, Regardless of Prior Docetaxel

The gist: The drug Xofigo (aka radium-223 dichloride) is often used to treat bone metastases in patients with castration-resistant prostate cancer. New research results show that it is safe and effective for these patients whether or not they have previously been treated with the chemotherapy drug docetaxel.

“Radium Ra 223 dichloride appeared safe and effective in patients with castration-resistant prostate cancer and symptomatic bone metastases regardless of whether they received prior docetaxel, according to a subgroup analysis from a randomized phase 3 trial.

“Results of the ALSYMPCA showed radium Ra 223 dichloride [radium-223 (Xofigo, Bayer)], a targeted alpha-emitter, extended OS compared with placebo in patients with castration-resistant prostate cancer and symptomatic bone metastases. The agent also appeared well tolerated.

“Researchers established prior docetaxel treatment as a trial stratification factor.

“In the prespecified subgroup analysis, researchers sought to assess the effect of prior docetaxel treatment on efficacy and safety outcomes.”

Sequencing Radium-223 and Docetaxel in Prostate Cancer

The gist: Scientists have found that the drug Xofigo (aka radium Ra223 dichloride) is “equally effective whether or not the patient has previously received chemotherapy with docetaxel.” Xofigo us used for men with metastatic castration-resistant prostate cancer (mCRPC).

“The novel radiopharmaceutical for prostate cancer, radium Ra223 dichloride (Xofigo), is equally effective whether or not the patient has previously received chemotherapy with docetaxel, a new analysis concludes.

“The product was approved last year for the treatment of metastatic castration-resistant prostate cancer (mCRPC) on the basis of results from the ALSYMCA study.

“Now, the ALSYMCA investigators report a prespecified analysis that shows that radium-223 is effective in these patients, regardless of previous docetaxel use. The report was published online October 17 in the Lancet Oncology.

“In an accompanying comment, Robert B. Den, MD, and W. Kevin Kelly, DO, from the Departments of Radiation and Medical Oncology, respectively, at Thomas Jefferson University in Philadelphia, say the new analysis shows that ‘men who have received previous docetaxel chemotherapy can be given radium-223 safely and its efficacy will be similar to patients who have not received previous docetaxel treatment.’

“But they also advocate caution. ‘The oncology community needs to proceed cautiously, since the ALSYMPCA trial was not able to identify the optimum sequence of administration of docetaxel and radium-233. Additionally, the trial was designed before the approval of enzalutamide and abiraterone acetate, so the clinical benefit of concomitant or sequential use of radium-223 with these drugs is unknown. Perhaps most intriguing would be the opportunity to integrate immunotherapy.’ “

Abiraterone Acetate/Prednisone in Metastatic Castration-Resistant Prostate Cancer: Final Analysis of Early-Access Protocol Study

The gist: In 2012, the U.S. Food and Drug Administration (FDA) approved a drug called Zytiga for the treatment of metastatic castration-resistant prostate cancer. It is prescribed along with the drug prednisone. Before the FDA’s approval, the Zytiga/prednisone combination was being tested in patients in a clinical trial. The trial was an “early-access” trial, meaning that it gave patients access to a very promising treatment that had not yet been approved. All patients involved had metastatic castration-resistant prostate cancer that had worsened after chemotherapy. Recently reported results from the trial showed no new safety concerns for the treatment.

“Abiraterone acetate (Zytiga) is approved for use in combination with prednisone in the treatment of metastatic castration-resistant prostate cancer. As reported by Sternberg et al in The Lancet Oncology, results of an open-label, early-access protocol trial initiated prior to approval indicated no new safety signals with abiraterone acetate plus prednisone given after progression on chemotherapy…

“The study, conducted in 23 countries, included 2,314 patients with metastatic castration-resistant prostate cancer progressing after taxane chemotherapy enrolled between November 2010 and September 2013. Patients received abiraterone acetate 1,000 mg/day and prednisone 5 mg twice a day in 28-day cycles until disease progression, development of sustained side effects, or approval and availability of abiraterone acetate in the country of residence…

“The investigators concluded: ‘No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients’ outcomes.’ ”

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.”