Darolutamide Delays the Spread of Prostate Cancer in Men with Non-Metastatic, Hormone-Resistant Disease.

Results from a Phase 3 clinical trial reveal that adding the androgen receptor inhibitor darolutamide to androgen deprivation (hormone) therapy (ADT) extends by 22 months (from 18.4 months to 40.4 months) the time men with hormone-resistant prostate cancer live without metastasis and without increasing the incidence of adverse events. The treatment also extended survival, time to pain progression, time until chemotherapy was needed, and kept patients alive and progression-free for longer periods than ADT alone, researchers reported.

The investigational drug darolutamide can help delay the spread of prostate cancer to other parts of the body in men with non-metastatic, hormone-resistant disease, according to results from the ARAMIS clinical trial. In addition, trial results showed that the drug appears to lack some of the side effects seen with similar drugs used to treat men with this form of prostate cancer.

Until recently, there had been no effective treatment options for patients with non-metastatic, hormone-resistant prostate cancer. These men have prostate tumors that continue to grow even after receiving androgen deprivation (hormone) therapy (ADT)  to keep androgen (testosterone) levels in the body extremely low or undetectable. But over the last 2 years, two drugs have been approved by the Food and Drug Administration (FDA) to treat this form of the disease and some researchers expect that, based on the results of this new trial, darolutamide may be next.

The darolutamide findings, from an interim analysis of the ARAMIS clinical trial, were published in the New England Journal of Medicine and presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco on February 14.

The drug has a very favorable safety profile. The incidence of side effects was generally similar between the darolutamide group and the placebo group, noted study coauthor Karim Fizazi, M.D., Ph.D., of the Gustave Roussy Institute, University of Paris, who presented the results in San Francisco. Darolutamide was not associated with a higher incidence of side effects such as seizures, falls, fractures, cognitive changes, or hypertension. The ARAMIS climical trial results “strongly support the use of darolutamide” in patients with non-metastatic, hormone-resistant prostate cancer, said William Dahut, M.D., head of the Prostate Cancer Clinical Research Section of the National Cancer Institute’s (NCI) Center for Cancer Research.

Darolutamide, jointly developed by Bayer and Orion, belongs to a class of oral drugs called androgen (testosterone) receptor inhibitors.  It prevents the binding of testosterone to the androgen receptor on a cell, thus blocking signals that prostate cancer cells require to grow and proliferate. In the body, these agents compete with androgens for binding to the androgen receptor, which reduces the ability of androgens to promote the growth of prostate cancer cells.

In 2018, the Food and Drug Administration (FDA) approved both apalutamide (Erleada) and  enzalutamide (Xtandi) for men with non-metastatic, hormone-resistant prostate cancer. In the clinical trials that led to these approvals, the drugs were shown to improve the median time from random assignment until the tumor spread or the patient died—known as metastasis-free survival—in men with this form of prostate cancer. Treatment with both drugs, however, was associated with side effects related to the central nervous system, including fatigue, falls, and cognitive changes. In both trials, treatment with the respective drugs more than doubled metastasis-free survival compared with men who received a placebo: 40 versus 16 months in the apalutamide trial and 36.6 versus 14.7 months in the enzaluatmide trial.

The ARAMIS trial, which was sponsored by Bayer and Orion Corporation—the co-developers of darolutamide—included men whose prostate-specific antigen (PSA) levels were rising at a rate that has been associated with an increased risk of metastasis and death in previous studies. Metastasis-free survival was the primary endpoint of the trial; secondary endpoints included overall survival and the amount of time until a patient’s pain worsened.

The randomized trial included more than 1,509 men with non-metastatic, hormone-resistant prostate cancer whose PSA levels were rapidly rising while receiving hormone therapy. These men were considered to be at increased risk of having the disease spread to other parts of the body. All participants received ADT plus either darolutamide or a placebo. At a median follow-up of 17.9 months, the median metastasis-free survival was 40.4 months for patients receiving darolutamide plus ADT, compared with 18.4 months for patients receiving placebo plus ADT. The risk of metastasis or death from any cause was reduced by 59%. While more than half of patients were alive at the time of the analysis, the interim analysis pointed toward a 29% reduction in the risk of death for patients taking darolutamide. Also, the treatment extended the time patients lived without disease progression — 36.8 months versus 14.8 months — representing a 62% reduction in the risk of disease worsening or death. The 3-year overall survival rates were 83% in the darolutamide group and 73% in the placebo group, the researchers found. The median overall survival has not yet been reached in the study. The median amount of time until a patient’s pain got worse was longer in the darolutamide group than in the placebo group (40.3 months versus 25.4 months). It lowered the risk of needing a chemotherapeutic medication by 57%. The time to first skeletal event — such as radiation therapy to the bone, bone fractures, spinal cord compression, or bone surgery — was also longer with darolutamide.

Darolutamide has a different chemical structure than apalutamide and enzalutamide whose structures as similar, which the study authors believe may explain why it has fewer side effects. Darolutamide basically does not penetrate the blood-brain barrier, whereas apalutamide and enzalutamide do. The low incidence of central nervous system-related side effects seen in the trial was consistent with its rodent studies. Side effects likely to be related to the drug reaching the central nervous system include fatigue, dizziness, cognitive impairment, and seizures, according to the researchers. There was no detectable difference in the incidence of these side effects between patients treated with darolutamide and those who received a placebo, he added, noting that patients with a history of seizures were not excluded from the trial. In the trial, fatigue was the only side effect that occurred in more than 10% of participants in either group. A low incidence of side effects is particularly important for men who do not have symptoms of the disease, researchers noted. The percentage of participants who stopped taking either the drug or the placebo because of side effects was similar, i.e. about 9%.

In the coming years, researchers and patients hope to learn more about patient preferences for darolutamide, enzalutamide, and apalutamide. For example, an ongoing clinical trial is comparing two of these androgen receptor inhibitors, darolutamide and enzalutamide in men with metastatic hormone-resistant prostate cancer to determine which drug patients prefer based on their responses to a questionnaire. Patients will first take one drug and then the other. In the meantime, darolutamide has already received Fast Track designation by the U.S. Food and Drug Administration for the treatment of non-metastatic, hormone-resistant prostate cancer patients.

The information above appeared in the National Cancer Institute (NCI) e mail periodical, NCI@updates.cancer.gov, dated March 15th, 2019.

Can God Use Cancer?

I recently received an e mail from the Cancer Treatment Centers of America (CTCA) entitled Health, Hope and Inspiration. These periodic e mails contain 30 minute interviews with Rev. Percy McCray, spiritual coordinator for CTCA. The latest interview entitled “Can God Use Cancer?” grabbed my attention. Rev. McCray’s immediate answer to the question was a resounding “yes”. During the interview, he cited a resource from CTCA entitled Cancer Ministry Scriptures, a compilation of Biblical references focused on leadership and inspiration, comfort, hope, God’s compassion, healing and strength, peace, and encouragement. This resource is similar to the section of this Godandprostate website entitled “Spiritual Medicines” to which I refer often. I was inspired to compile the latter after being told first-hand of God’s healing of a woman I knew from a brain tumor. Her son had compiled a short list of scripture verses which his mother cited and prayed daily in addition to taking her prescribed medicines. Her healing was confirmed by her surgeon at Johns Hopkins in Maryland.

During the interview with Rev. McCray, he focused on Philippians 1:12 wherein the apostle Paul cites a list of negative circumstances such as imprisonments, beatings, shipwrecks etc. but which all eventually had positive outcomes, namely that God used these events to further the propagation of His divine plan.  Paul writes “now  I want you to know brethren, that my circumstances have turned out for the greater progress of the gospel.” The things that happened to the apostle Paul and to ourselves can serve as a furtherance of God’s plan for us  both personally and impersonally to those with whom we come into contact. Thus, God can use a cancer diagnosis for positive results.  When one receives the initial diagnosis of cancer, there is often an emotional shock. But soon, we can realize that God did not give us the cancer but He has empowered us to accomplish something positive with this diagnosis. Cancer can open doors to share what God has done in our lives and the abundant life we have in Him through faith in Jesus. In John 10:10, Jesus proclaims  that He comes to give us an abundant life. But a translation of the word “abundant” means an ability to rise above our circumstances. Had we never received a cancer diagnosis, we may have never considered it a ministry. God can show us elements of ourselves or ministry to others thru cancer.  We are led to seriously consider the main bedrock purposes of our life. God can show us our strengths and especially our weaknesses thus enabling us to see that He Himself is the source of all our needs. We can see ourselves as little children who, when hurt, run to a loving parent for comfort. But now we see that God is that loving Father when we run to Him in faith and need. God’s promises in Scripture become alive as never before.

So what are the changes in my life and attitudes toward myself and others around me that have occurred as a result of a cancer diagnosis? Do we now focus more on actions that may have eternal results or consequences? These are questions we should prayerfully consider. For me personally, this website would never had been written had God cured me of prostate cancer during my initial surgery in 1995. But His care continues to permeate my life as it can any of us who have a personal relationship with God through Jesus Christ as described in the following link. In conclusion, may we be able to say with certainty that “we know that God causes all things to work together for good  to those who love God, to those who are called according to His purpose.” (Romans 8:28).