2018 Blog

Seven Causes of Elevated PSA Levels

bjgabrielsen : December 5, 2018 10:13 pm : 2018, Diagnostics, Genetics, Imaging, General Patient Information
  1. Age. In general, a normal PSA range for men in their 40’s is 0-2.5 ng/mL; men in their 50’s, 0-4 ng/mL; 60’s, 0-4.5 ng/mL; and 70’s, 0-6.5 ng/mL. Ethnicity may shift these values slightly as well.
  2. Prostate size. A man with a larger-than-normal prostate gland may have a higher PSA level. A digital rectal exam by your physician will detect this.
  3. Prostate inflamation. Bacterial infections e.g. prostatitis produce inflamed, tender or swollen glands thereby elevating one’s PSA level.
  4. Benign Prostatic Hyperplasia (BPH). BPH is an enlarged prostate and differs from simply having a larger-than-usual gland. It is common in men over 50 and may make urination or ejaculation difficult. Additional tests can confirm BPH.
  5. Urinary tract infection or irritation. This infection as well as irritation caused by medical procedures involving the urethra or bladder may cause the gland to produce more PSA. If any such procedures have been performed, give the area some time to heal before running a PSA test.
  6. Prostate stimulation. Stimulation such as through sexual activity, ejaculation or even having a digital rectal exam by your physician may affect PSA results.
  7. Medications. Some medications can artificially lower the PSA, such as finasteride (Proscar or Propecia) or dutasteride (Avodart). Remind your doctor of any of these medications you may be taking so they can factor them in when assessing your PSA results.                                                                                                                                                  This information was obtained from the Prostate Cancer Foundation, www.pcf.org.


Rubraca (Rucaparib) Shrank Tumors in Nearly Half of Advanced Prostate Cancer Patients with BRCA Mutations.

bjgabrielsen : November 8, 2018 8:36 pm : 2018, Treatment Information

Rubraca (rucaparib), Clovis Oncology‘s oral PARP inhibitor, shrank tumors in 44% of metastatic hormone-resistant prostate cancer (mCRPC) patients with BRCA mutations included in the Phase 2 TRITON2 clinical trial. The treatment, which is already approved for ovarian cancer, also reduced PSA levels — a biomarker of prostate cancer — in 51.1% of patients with BRCA mutations. The findings were presented recently at the European Society of Medical Oncology (ESMO) 2018 Congress  and other meetings by Wassim Abida, a medical oncologist at the Memorial Sloan Kettering Cancer Center in New York, and principal investigator for the Phase 2 study.

About a quarter of advanced prostate cancers show mutations in BRCA1BRCA2 or other genes encoding proteins that repair damaged DNA. These tumors are more sensitive to further DNA damage, and often respond well to treatments that block other proteins involved in aiding DNA repair. The PARP enzymes are more involved when BRCA proteins are not functioning properly, and PARP inhibitors have shown great promise in breast and ovarian cancer patients with BRCA mutations. Now, data from the TRITON2 Phase 2 trial (NCT02952534) shows that Rubraca also is effective in prostate cancer patients with such mutations.

The Phase 2 trial is testing the efficacy and safety of Rubraca (600 mg twice a day) in 85 mCRPC patients who have inherited or acquired BRCA mutations, or in one of the 13 DNA repair genes known to increase susceptibility to PARP inhibitors, and who were already treated with androgen receptor-directed therapy (e.g. Xtandi or Zytiga) and taxane-based chemotherapy (e.g. taxotere). Depending on their disease and mutation status, patients were divided in three groups: those with BRCA or ATM mutations and with measurable disease; those with BRCA or ATM mutations without measurable disease; and, those with mutations in other DNA repair genes, with or without measurable disease. The primary goal of the study is to determine the proportion of patients with measureable disease who respond to Rubraca, and those without measureable disease who achieve a significant lowering of their PSA levels. Secondary measures include duration of response, time to disease progression or death, overall survival and safety measures.

After a median follow-up of 5.7 months, 46 out of 85 patients were evaluable for responses. Among the 25 patients with BRCA mutations, 44% had seen their tumor shrink, after only a median of 3.7 months on treatment. At the time of the analysis, more than half of patients were still responding to Rubraca. The results also showed that 51.1% of patients with BRCA  mutations saw a reduction in their PSA levels. The most common adverse events were fatigue, nausea, anemia, and constipation. Five patients discontinued Rubraca due to a treatment-related adverse effect, and one patient died of disease progression.

Enrollment in TRITON2 is ongoing. The trial expects to evaluate about 160 patients from at least 100 worldwide locations, and to study other mutations besides BRCA1/2.

Findings from the trial have led the U.S. Food and Drug Administration to grant breakthrough therapy designation to Rubraca as a treatment for mCRPC patients with BRCA mutations, earlier this month.This FDA designation is given to speed the development of medications that might treat serious conditions and potentially provide an improvement on available therapies.  It has now been shown that PARP inhibitors are a validated therapeutic class in oncology in multiple tumor types, and these new data underscore the benefit that Rubraca may provide for men with advanced, BRCA-mutant castration-resistant prostate cancer.

This information represents a compilation of two articles published in the 10/24/18 Prostate Cancer News Today.


As Christians, Do We Believe That Jesus Can Do What He Has Promised?

bjgabrielsen : September 30, 2018 9:49 pm : 2018, Encouragement

Today I awaited the result of my next test for prostate-specific antigen, better known as PSA. In the past, this wait has many times been accompanied by some degree of anxiety. But this time, I had purposed in my heart and mind to release the outcome to the Lord’s care whatever the result may be. Which reminded me of a recent devotional from Dr. David Jeremiah entitled “I Didn’t Know”.  It focused on the familiar story of Jesus’ disciples being in a boat and encountering a storm.

During the three years the disciples spent with Jesus, they had personally witness Him multiply five loaves and two fish to feed thousands, heal the sick and lame, cast out evil spirits and even raise the dead. Many times the disciples seemed to say “I didn’t know He could do that”. Another thing they didn’t know was that Jesus could walk on water – and allow them to do the same. In this instance, during a vicious storm, they spotted Jesus walking on the water toward them. Peter boldly said, “Lord, if it is You, bid me to come to You on the water.” (Matt: 14:28)  I recently read that the word “if” could better be translated by the word “since“. The word “if” can sometimes carry with it some degree of uncertainty. But the term “since Jesus said it,”  implies a higher degree of trust.  Jesus implored Peter to come but he began to sink in the waves when he took his eyes off of Jesus. However, Matthew 14:31,  records “and immediately Jesus stretched out His hand and caught Peter and said to him, ‘O you of little faith, why did you doubt?'”

Life with Jesus is a never-ending discovery of His love and power if only we will trust Him. If we practice the commands to “trust and obey”, a beautiful cycle begins. According to Dr. Charles Stanley, “trusting the Lord makes obedience easier, and obedience produces ever-increasing trust.” Perhaps we may have never trusted God completely for unusual needs, medical or otherwise. May we explore, trust and discover life with a miracle-working Lord who can deliver what He has promised. Remember the words of this familiar hymn. “Tis so sweet to trust in Jesus, just to take Him at His Word. Just to rest upon His promise, just to know “thus saith the Lord.” To start a personal relationship with God, see the following link. By the way, my own test result came back as good as I could have hoped for.



Can God Use Our Prostate Cancer? Yes He Can!!!

bjgabrielsen : September 20, 2018 11:21 pm : 2018, Encouragement

New day breaking over Balestrand, on the northern shore of the Sognefjord, west coast of Norway; photo BJ Gabrielsen.

As I write this post, it constitutes the 1,000,000+ hit on this website which I can only trust has been a help and a blessing to some of you since I was prompted to share my personal story via a blog.

As I write it, it has been 23 years since I was first diagnosed with prostate cancer. While I am classified as having advanced disease, I am asymptomatic, am feeling well and my PSA is undetectable. But there will probably come a day when I will have to read my own website admonitions and apply them to my own life. Can God use my (our) disease to glorify Him? Emphatically, Yes!

What has God told me to do about my condition? The answers are three-fold: a) to yield it to Him; b) to trust Him completely in what He has told me in His Word, and, c) be cognizant of any opportunity to share my story with others that regardless of any outcome, God is to be glorified. In the Old Testament, the prophet Elijah was alone told by God to confront the hundreds of prophets of the false god Baal, whom many of the Israelites had been worshipping as instructed by the evil King Ahab and Queen Jezebel. First, Baal’s prophets placed a sacrificial ox on an altar and in a vain attempt to induce Baal to ignite the sacrifice, they invoked the name of their god to the point of yelling, and cutting themselves for hours to no avail. It now was Elijah’s turn and he went several steps further. He put his ox on a stone altar, made a trench around it, put wood on top of the altar, laid the ox on the wood, poured several pitchers of water on the ox and saturated the wood around it. He did the latter not once but three times. Then he filled the surrounding trench with water. The goal was of course to ignite the burnt offering as a sacrifice to God. Then interestingly enough, Elijah did not pray the obvious prayer namely for fire to come down and ignite the offering which is what one might expect to pray. He merely prayed, “O Lord, the God of Abraham, Isaac and Israel (Jacob), let it be known that You are God in Israel and that I am your servant and that I have done all these things at Thy word. Answer me, O’ Lord, answer me that this people may know that You O’ Lord are God and that You would turn their heart back again.” (I Kings 18: 36-37). Notice that Elijah did not pray specifically for fire to fall. But it did, spontaneously consuming the offering, the wood, the stones, the dust and licked up all the water in the trench.

How does this relate to offering my prostate cancer? Like Elijah used a sacrificial ox to demonstrate God’s power, I am to lay my body down as an offering according to Romans 12:1 which states “I beseech you therefore, by the mercies of God to present your body as a living sacrifice, holy and acceptable to God which is your reasonable service of worship.” I should then be attentive to whatever circumstance I would find myself where my personal disease sacrifice could be viewed by others including any medical personnel. While it is normal to do so, I should not pray that God would heal my disease according to my plans and scenario. Remember Elijah did not pray for God to send fire and devour the animal sacrifice. But instead, I should pray like Elijah, listen and follow whatever God has told me, and pray that God would somehow demonstrate His presence and power through my disease and thereby be glorifed. Then step back and leave the results to Him.

Jesus Himself made a similar prayer in John 12:23-28. He knew He would soon undergo a painful death by crucifixion and be totally cut off from God, His Father and bear the penalty of the sins of everyone who ever lived and would ever live. Jesus demonstrated His humanity by saying in v. 27, “Now my soul has become troubled and what shall I say, ‘Father save me from this hour?'” In other words, He asked God if He could be spared all this pain and suffering? But then like Elijah, He concludes “But for this purpose I came to this hour. Father, glorify Thy Name.'” Like Elijah and Jesus, may the same be said of us. God can indeed be glorified through our disease state. If you, the reader, cannot identify clearly with this scenario, you too can have an intimate and personal relationship with God much like Elijah. See the following link.

Thank you all for putting this site over the millonth mark.


What to Do with Our Worry

bjgabrielsen : September 9, 2018 9:03 pm : 2018, Encouragement

When all is going well, I don’t usually get anxious except perhaps when I am due for my next PSA test or scan.  Faced with upcoming medical decisions and testing, I confess that in the past I have had a bad habit of anticipating the worst scenario because then the final outcome can only be an improvement. I know that has been a very negative and distrusting way of thinking. Worry often creeps into all of our lives seemingly without warning. However, over the last 23 years, I have learned to release these events and results to God. So the following might be a good word for all of us.

When we worry we are focused on possibilities that have not yet happened or are beyond our control. In the weakness of our fears, we can be comforted knowing nothing comes into our lives apart from God’s knowledge. It’s an opportunity to accept His offer to be our strength and hope regardless of what happens.

I know it can sound like a cliche but remember God is in charge. Nothing happens beyond the knowledge and control of God. When we worry, we are actually acknowledging the truth that in ourselves we are not adequate to meet the demands of life. This is our moment to remind ourselves of some important truths about God. He is everywhere. “Can a man hide himself so I do not see Him, and do I not fill the heavens and the earth declares the Lord?” (Jeremiah 23:23-4). He knows everything. “The Lord looks from heaven and sees all the sons of men” (Psalm 33:13). He is all-powerful. “Jesus said ‘with men this is impossible but with God all things are possible.'”(Matthew 19:26).

Believe He can carry our burdens. But how do we place our cares on the shoulders of God? The answer lies in what we are trusting – in our feelings or in the character of our all-powerful, trustworthy God. “Cast your burden upon the Lord and He will sustain you. He will never allow the righteous to be shaken.” (Psalm 55:22).

Admit He is greater than our fears. In Psalm 31, David wrote of being forsaken by his friends and attacked by his enemies. Yet he could say in verse 15 “my times are in Your hand”. David knew God’s goodness and love from experience.

Trust He can sustain us. Advertisements for most things from investments to medicinals all come with disclaimers. Some ads on TV and radio recite disclaimers so fast their words are intelligible. In this broken world we have no guarantees except that God and His Word can be trusted. He wants us to draw on the depths of His love and grace.

Count on Him to never forsake us. If we are God’s children, we are never apart from our Father’s care. “He Himself has said ‘I will never desert you nor will I ever forsake you.” (Hebrews 13:5).

If you cannot personally relate to these truths and principles, you can have a personal relationship with the God who stands behind them. See the following link.

The above was adapted from the Our Daily Bread monthly devotional series, August, 2018.


Gadolinium Contrast Agents in Prostate MRI’s and the New FDA Warning

bjgabrielsen : September 4, 2018 12:42 am : 2018, Diagnostics, Genetics, Imaging

For the most part, MRI imaging for prostate cancer is safe. In some cases, contrast agents are needed to be injected into the human body in order to get a better picture or scan. Many of the contrast agents utilized contain the heavy metal, gadolinium. These injected agents help physicians see internal organs, blood vessels and other tissues more clearly.

In late 2017, the FDA declared that all gadolinium-containing contrast agents must carry the warning about how they could be retained in the body and potentially cause kidney injury. Most of the gadolinium is eliminated by the kidneys. If one’s kidney function is normal, there has been no direct link with these contrast agents to any specific health issue.  The brand name Gadavist (gadobutrol) is often used for MRI screening of prostate cancer and active surveillance. Much lower levels of this agent are used compared to other agents. The FDA is now asking the manufacturers of gadolinium agents to conduct more human and laboratory studies to determine the safety of these agents. Thus far, the one real adverse effect noticed with these agents is in a small group of patients with pre-existing kidney failure, a condition known as nephrogenic systemic fibrosis. More recently, researchers in Belgium and Japan expressed concern that gadolinium-based contrast agents showed preliminary evidence of depositing in the part of the brain called the cerebellum.

Here is a list of eight (8) of the most widely used gadolinium contrast agents and their brand and generic names and levels of concern. The following three have lower levels of retention and are of less concern; a) Dotarem (Gadoterate Meglumine); b) Gadavist (Gadobutrol); and, Prohance (Gadotridol). The following five have high levels of retention; a) Eovist (Gadoxetate Disodium); b) Magnevist (Gadobenate Dimeglumine); c) Multihance (Gadobenate Dimeglumine); d) Omniscan (Gadodiamide); and e) Optimark (Gadoversetamide).

The body retains less gadolinium when using agents that have what is known as a macrocyclic (large rings) chemical structure, as in Dotarem, Gadavist and Prohance. Gadolinium agents that have a linear chemical structure have higher levels in the body after using them.

So the next time you have an MRI with contrast, inquire which of the gadolinium agents are being used. If it is one with linear structure or higher retention, one should ask for alternatives or seek out another imaging facility.

This post is an excerpt from an article written by Mark Moyad, MD, MPH, Jenkins / Pokempner Director of Alternative Medicine, University of Michigan Medical Center. It was published in the summer 2018 issue of the Prostate Digest, Volume 21, Issue 2, published by the Prostate Cancer Research Institute.

P.S. So now you know how to respond when you see one of those notorious lawyer ads on TV asking if you “have ever taken an MRI with contrast and developed _______. You may be entitled to substantial compensation.”


One of the Most Admirable Young Men I’ve Ever Met

bjgabrielsen : August 27, 2018 10:00 pm : 2018, Encouragement

I know this website is focused on providing information to men whose prostate cancers are at any stage. Hopefully most of us may not die of prostate cancer although in my own case, that is definitely a possibility. For myself and I know for many of you as well, our Christian faith and our personal relationship with God plays a most significant role. Some years ago, I came to know an extraordinary young man who was stricken with Duchenne’s Muscular Dystrophy and has been in a wheelchair since the age of 12. He is now 26 and his disease is now seriously threatening his earthly life. Through the years, he has received a college degree, has penned at least two books and is an active blogger on sports especially football as well as spiritual issues. In short, Jonathan is one of the bravest, most honest and admirable men I have ever met. As an inspiration to all of us, I have provided this link to his most recent blog.    http://jonathansperspectiveongod.blogspot.com/2018/08/jonathans-perspective-on-heaven.html?m=1

If any of you wish to know more about entering into a personal, life-changing relationship with God and receive the promise of eternal life in a new heaven and a new earth with a new perfect body and experience the peace and strength that Jonathan possesses in this life, see the following link from this website.



Some Advanced Prostate Cancer Patients May Respond Well to Keytruda Immunotherapy.

bjgabrielsen : August 20, 2018 9:44 pm : 2018, Treatment Information

Immunotherapy with Keytruda (pembrolizumab) may be an effective way to treat some cases of advanced prostate cancer according to a preliminary study conducted at Oregon Health and Science University – Knight Cancer Institute. Findings were published in the journal Oncotarget in a paper entitled “Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer.” Keytruda is a monoclonal antibody that blocks the PD-1 receptor on the surface of immune T-cells, allowing them to recognize and destroy tumor cells. The FDA-approved drug has been shown to work well in melanoma and lung cancer but has so far not demonstrated much anti-tumor activity in prostate cancer.

Researchers administered Keytruda in ten (10) men with metastatic prostate cancer who had received androgen deprivation therapy or the androgen receptor antagonist Xtandi (enzalutamide) but failed to respond to it. Three of the 10 men who participated on the trial responded remarkably well to Keytruda treatment. Prostate-specific antigen (PSA) levels in their blood, an early measure of treatment response, dropped rapidly and dramatically from 46, 71, and 2,503 ng/ml respectively to less than 0.1 ng/ml. In addition, two of the three men saw their tumors shrink and reported a reduction in cancer-related pain to the point of not needing their opiate pain medication. Finally, the three patients who responded to Keytruda remained free of cancer progression at 30, 55 and 16 weeks of follow up, respectively.

It is still unclear why only three of the ten men who participated in the clinical trial responded to Keytruda while others showed no signs of clinical benefit. It is not yet possible to conclude that blocking PD-1 signaling can improve survival in men with metastatic prostate cancer, or to predict which patients will respond to treatment. More research is needed to better understand the mechanisms by which Keytruda reduces prostate cancer and which factors may influence the therapeutic effect of the drug. Additional patients have been enrolled in this clinical trial.

For a review of immunotherapy in prostate cancer, see the following link.


Phase 2 Trial of Potential Prostate Cancer Vaccine, ProscaVax, Soon to Enroll Early-Stage Patients

bjgabrielsen : August 17, 2018 12:25 am : 2018, Treatment Information

OncBioMune Pharmaceuticals will soon start a Phase 2 clinical trial of its investigational vaccine ProscaVax in men with early-stage prostate cancer under “active surveillance”. ProscaVax consists of a combination of the PSA protein produced by the prostate gland with the cytokines interleukin-2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). [Cytokines are molecules that participate in immune responses.] This will be the first time that prostate patients will be treated with a vaccine rather than waiting for disease progression or being exposed to more invasive treatment options that frequently are accompanied by unpleasant side effects such as incontinence and/or impotence. Scientists will evaluate whether the vaccine leads to a change in prostate cancer progression compared to patients on “active surveillance” in which disease progression is monitored before other strategies such as surgery or radiation therapy are considered. PSA doubling time and adverse effects will also be assessed.

Treatment arm-patients will start with a 4-month induction period, being given six (6) doses of ProscaVax at weeks 1, 2, 3, 7, 11, and 15. This period will be followed by maintenance injections once every month and alternating between low-dose IL-2 alone and the ProscaVax vaccine for six months.

OncBioMune reported results of a Phase 1a/1b study in January, 2018 showing that ProscaVax reduced tumor growth in 70% of recurrent prostate cancer patients after a minimum of 31 weeks of treatment. This result added to previously reported positive safety data. Trial results at 19 weeks of treatment also found that ProscaVax stopped disease progression in 80% of patients.

The single-site trial is expected to finish in August, 2022. It will be conducted at Beth Israel Deaconess Medical Center in Boston, MA and includes the Dana-Farber Cancer Institute. Information about this trial was published in the July 16th, on-line edition of Prostate Cancer News Today to which readers of this website are urged to subscribe.


Both Enzalutamide and Apalutamide Delay Prostate Cancer Progression in Men with Non-Metastatic Hormone-Resistant Prostate Caancer

bjgabrielsen : August 12, 2018 9:42 pm : 2018, Treatment Information

In catching up on some news from a few months ago, I realized that much had been written recently about treating men with an early stage of advanced  prostate cancer. So here is some information in addition to the following posts; The FDA Approves Apalutamide for Some Men with Prostate Cancer; and  Xtandi Extends Metastasis-Free Survival in Hormone-Resistant Men with Rising PSA according to Phase 3 Study.

Over the course of prostate cancer progression, there can come a time during which the cancer is progressing, but there are no treatments known to improve survival.  One of these “empty spaces” is when men who are being treated with androgen deprivation therapy (ADT) see their PSA levels begin to rise (indicating the cancer has become resistant to ADT and is starting to grow again), but no metastases are visible yet on scans.  This clinical state is termed “non-metastatic hormone-resistant prostate cancer” (non-metastatic CRPC).  Many of these men will ultimately go on to develop metastases and lethal prostate cancer.  Until today, there were no other options and these men often just continued to receive ADT despite its diminishing benefit.

At the 2018 ASCO Genitourinary Cancers Symposium, held February 8-10 in San Francisco, California, results from two randomized phase 3 clinical trials, SPARTAN and PROSPER, may have filled this empty space.  Enzalutmide (Xtandi®) and Apalutamide (Erleada®; ARN-509) are two highly similar hormonal treatments that when added to ADT (or whatever treatments were already being used) were found to significantly delay the onset of metastases and several other measures of cancer progression in men with non-metastatic CRPC.

In the PROSPER trial, investigator Maha Hussain, MD (Northwestern University), tested the addition of enzalutamide vs. placebo in 1,401 non-metastatic CRPC patients who were continuing to receive ADT despite a rapidly rising PSA.  Enzalutamide was found to delay the time to metastatic disease by 22 months on average, compared with placebo.

In the SPARTAN trial, investigator Eric Small, MD (University of California, San Francisco), tested the addition of apalutamide vs. placebo in 1,207 non-metastatic CRPC patients with rapidly rising PSA,  in addition to whatever treatment the men were already receiving (mostly ADT). Apalutamide was found to delay the time to metastatic disease by over 24 months on average.   The full results from the SPARTAN study were simultaneously published in the New England Journal of Medicine.

This could be amazing news for patients with CRPC. “We don’t yet know if either apalutamide or enzalutamide increases the survival duration in these patients, although early indication is in that they will,” said Philip Kantoff, MD, Chairman of the Department of Medicine at Memorial Sloan Kettering Cancer Center, who led the discussion on the trials at the Symposium.  “Patients do need to be aware that these treatments when used early, can cause greater treatment exposure and greater chance for toxicity including a small chance of unexplained death.  Nonetheless these trials may change practice patterns in a major way and provide treatment opportunities for men with no current effective therapies.”

These two treatments are highly similar oral medications, differing chemically by only a single atom.  They have since been separately licensed and developed by different pharmaceutical companies, namely Astellas Pharma (enzalutamide) and Janssen (apalutamide).  Apalutamide is a new medicine, whereas enzalutamide is already FDA-approved for metastatic CRPC.  Both of these treatments are now under review by the FDA for use in non-metastatic CRPC, and decisions – and the change in practice that will accompany an FDA approval — are expected very soon.

For additional information, see the Prostate Cancer Foundation Feb. 28th Newsletter.


The FDA Approves Apalutamide for Some Men with Prostate Cancer

bjgabrielsen : August 11, 2018 10:51 pm : 2018, Treatment Information

I realize this is somewhat old news but I’d like to share it anyway. On February 14, the Food and Drug Administration (FDA) approved apalutamide (Erleada) for men with prostate cancer that has not spread (non-metastatic) and is resistant to standard hormone therapy, also called androgen deprivation therapy (ADT). In the clinical trial that led to its approval, treatment with apalutamide decreased the risk of metastasis or death by more than 70% compared with placebo.

In the phase 3 trial (dubbed SPARTAN) that led to the FDA approval, men with hormone-resistant prostate cancer and no metastatic disease detectable by standard imaging tests were randomly assigned to receive apalutamide or placebo in addition to ongoing ADT. All participants were at high risk of metastasis based on rapidly rising prostate-specific antigen (PSA) levels. The study was sponsored by Janssen Pharmaceutical Companies, the manufacturer of apalutamide.

The median length of time from the start of treatment to when tumors spread (metastasis-free survival) or the patient died was 16 months in the placebo group and 40 months in the apalutamide group. Men treated with apalutamide also went longer without worsening symptoms of cancer progression. Even when their cancer progressed on apalutamide and they went on to receive another therapy, these men had longer time to progression with the subsequent treatment than men in the placebo group. The median length of time patients were alive after the start of treatment (overall survival) was 39 months for those who received placebo and had not been reached at the time of the study analysis for those who received apalutamide. An early analysis suggests that apalutamide may reduce the risk of death from prostate cancer, but longer patient follow-up is needed before the researchers can confirm this.

Apalutamide is the first drug to be approved by FDA based on an improvement in metastasis-free survival. Traditionally, most approvals are based on an improvement in progression-free survival or overall survival.

“These are very dramatic results and, in many ways, exceeded our expectations,” said lead investigator Matthew Smith, M.D., Ph.D., of Massachusetts General Hospital Cancer Center.  “We’re learning that using hormone therapy earlier in men with prostate cancer can delay metastasis and probably improve survival. But the balance of benefits and potential side effects will need to be evaluated on a patient-by-patient basis,” said William Dahut, M.D., head of the Prostate Cancer Clinical Research Section of National Cancer Institute’s Center for Cancer Research (NCI-CCR).

While apalutamide—and, potentially, enzalutamide (Xtandi)—gives men with non-metastatic hormone resistant disease a new treatment option, this patient population may decrease in the future, Dr. Dahut noted. That’s because traditional imaging techniques such as a CAT scan may not be able to detect tiny metastatic tumors, he explained. But a technique being used in research studies called molecular imaging  can catch smaller tumors. If molecular imaging tests become part of clinical care, more men with prostate cancer might be classified as having metastatic disease. “It’s highly likely that apalutamide would be active in men with metastatic hormone-resistant prostate cancer, Dr. Dahut speculated. Trials to evaluate apalutamide in this patient population are already underway, Dr. Smith noted.

For additional information, see the March 8th, 2018 NCI Cancer Currents blog.

Related blogs describing apalutamide were published on this website. See February 16th, 2018 and  November 10th, 2017 posts.



Xtandi Extends Metastasis-Free Survival in Hormone-Resistant Men with Rising PSA according to Phase 3 Study.

bjgabrielsen : July 20, 2018 1:02 am : 2018, Treatment Information

Men with nonmetastatic, castration (hormone)-resistant prostate cancer (CRPC) and a rapidly rising prostate-specific antigen (PSA) level are at high risk for metastasis. Currently, only one recently approved treatment, Erleada® (apalutamide), is available to these patients. Xtandi®, an androgen receptor inhibitor, is an approved treatment for metastatic CRPC patients. It has been shown to delay disease progression and prolong these patients’ overall survival.  In a recent article published in the June 28th, 2018 issue of the New England Journal of Medicine, researchers hypothesized that enzalutamide (Xtandi®), which prolongs overall survival among patients with metastatic, hormone-resistant prostate cancer, could also delay metastasis in men with nonmetastatic, hormone-resistant prostate cancer and a rapidly rising PSA level. In this double-blind, phase 3 PROSPER trial, asymptomatic men with nonmetastatic, hormone-resistant prostate cancer and a PSA doubling time of 10 months or less and who were continuing androgen-deprivation (hormone) therapy received enzalutamide (at a dose of 160 mg) while men receiving only placebo and standard hormone therapy were randomized in a 2:1 ratio. The primary end point of the study was metastasis-free survival, the length of time a patient lives without cancer spreading or until death from any cause. Secondary goals included extension of the time to PSA progression and to the first use of a subsequent anticancer chemotherapy, patients’ overall survival, and safety.

A total of 1401 patients (median PSA doubling time, 3.7 months) were enrolled. As of June 28, 2017, a total of 219 of 933 patients (23%) in the enzalutamide group had metastasis or had died, as compared with 228 of 468 (49%) in the placebo group. The median metastasis-free survival was 36.6 months in the enzalutamide group versus 14.7 months in the placebo group. The time to the first use of subsequent chemotherapy was longer with enzalutamide treatment than with placebo (such therapy was used in 15% vs. 48% of patients) as was the time to PSA progression (37.2 vs. 3.9 months.) At the first interim analysis of overall survival, 103 patients (11%) receiving enzalutamide and 62 (13%) receiving placebo had died. So median overall survival had not been reached. However, the researchers noted that more patients receiving the combination therapy died without detectable development of metastasis than was seen in the placebo group. In these patients, no trend regarding the cause of death was found, and only two deaths were considered to be related to Xtandi treatment. The researchers noted that these patients were elderly, with a median age of 80 years in the Xtandi group and 81 years in the placebo group, and they had a high burden of other coexisting conditions. Subsequent follow-up and additional interim analysis are expected to clarify the benefits of Xtandi® in patients’ overall survival in the PROSPER study.

Conclusions from this PROSPER clinical trial indicated that in men receiving the combination therapy the time a patient remained alive and metastasis-free was significantly extended by nearly two years (21.9 months), the time to PSA progression by almost three years (33.3 months), and the time to the first use of chemotherapy by nearly two years (21.9 months), compared to single standard therapy. In men with nonmetastatic, hormone-resistant prostate cancer with a rapidly rising PSA level, enzalutamide treatment led to a clinically meaningful and significant 71% lower risk of metastasis or death than placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, (NCT02003924).

As mentioned above, these findings were recently published (“Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer”) in the New England Journal of Medicine and also summarized in the July 5th Prostate Cancer News Today. (I strongly encourage readers to subscribe to this valuable email resource.)



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