PROMISE: A Clinical Trial of Inherited Genetic Factors Impact on Prostate Cancer Risk and Treatment Involving Free Genetic Testing.

It is known that prostate cancer may be written in some men’s genes, but so are instructions for discovering new treatments and understanding family risk. If we want to better understand prostate cancer, we have to better understand genes. That’s why the genetic information of prostate cancer patients is so important. This information is the next step in the collective fight against the disease. Yet, while 1 in 9 men will get prostate cancer and more than 4 million American men are currently living with the disease, genetic information is only beginning to be used for prostate cancer.

The PROMISE study is being launched to change all that. PROMISE seeks to learn more about the role genes can play in improving outcomes and/or treatments for prostate cancer patients. It will help understand how prostate cancer care can be tailored precisely based on a patient’s unique genetic profile. This means better information, testing and choices for you and others like you.

PROMISE research will examine how information about particular genetic profiles can:

a) Influence the susceptibility of men to prostate cancer;
b) Impact the effectiveness of existing treatments;
c) Improve guidance for different and/or new treatment options; and,
d) Suggest precise areas to explore for new discoveries.

How PROMISE works
PROMISE is completely free. Patients continue with their current provider and don’t even need to leave home to participate. Register online and we’ll send a simple, home-based DNA test kit. Just provide a saliva sample and return it via prepaid U.S. mail. The kit will screen for one of 30 cancer risk genes. We’ll send you the results and will provide a licensed genetic counselor to help you understand your results. You will learn if you have any gene mutations that might affect your care plan. The results may inform you of available treatment options and previously unknown risks of family members developing cancer. PROMISE will also create a new mechanism to communicate with prostate cancer patients on an ongoing basis to help connect them with new trials and treatments as relevant clinical trials are opened and approved for prostate cancer.

Benefits of joining the PROMISE study
Prostate cancer patients who join PROMISE will:

Receive free genetic testing and counseling that will help you learn important new information about genetic factors in your cancer and discover if you have a critical gene mutation that may impact your care plan.
Receive the most current information about new research, clinical trial opportunities, and treatments approved by the FDA. This information is sent via regular newsletters and updates.
Help family members understand their own risk of cancer and risk for future generations.
Make an important contribution to advancing research & understanding of prostate cancer by providing essential genetic information and long-term outcomes that are not available anywhere else.
Learn more
PROMISE is supported by a group of mission-driven nonprofit organizations. No pharmaceutical firms or any commercial interests are supporting this research. Participation is free and easy. Patients remain under the care of their current doctor. Patient’s don’t even need to leave home. Measures are in place to ensure safety, privacy and security.

Talk with your doctor about PROMISE and visit You can help win the fight against prostate cancer.

This information came from Zero-the Project to End Prostate Cancer

List of Prostate Cancer Drugs Approved or Under Development.

I have been compiling a list and brief description of such drugs as I learn about them from the scientific literature or other reliable sources. While my list of therapeutic agents under various stages of clinical development may not be complete, one can always search the site Recently three new therapies under development for advanced prostate cancer were added to my list, namely CCS1477, ARV-110 and most important, lutetium-177-PSMA. This list is always available from the website’s home page at the bottom.

Decipher Can Help Predict Metastasis and Whether Hormome Therapy is Needed in Recurrent Cancer.

Recurrent prostate cancer is usually treated with radiation alone or with the addition of hormone therapy. Doctors currently use certain criteria—like tumor grade and PSA level—to recommend whether patients with recurrent prostate cancer should get hormone therapy in addition to radiation. But studies have shown that these characteristics aren’t very good at identifying people who truly need the combination treatment. Because hormone therapy can cause distressing side effects—including hot flashes, loss of energy, and loss of sexual desire—the treatment is typically reserved for patients with aggressive cancer that is more likely to spread. Therefore it’s currently challenging to determine which patients have aggressive cancer that may require the addition of hormone therapy.

A new study found that the genetic biomarker test, called Decipher, may have the ability to do just that. The test looks at the activity of 22 genes in prostate tumor tissue and calculates a “risk of metastasis” score ranging from 0-0.45 (low), 0.45-0.6 (intermediate) and 0.6 – 1.0 (high). Using data from an NCI-sponsored clinical trial, researchers found that people with higher Decipher scores were more likely to have cancer that spread years later and to die from the cancer. The results, published February 11 in JAMA Oncology, also showed that hormone therapy helped people with higher scores live longer but was far less helpful for those with lower scores. For a more specific description of the Decipher test scores, see the following link to an article published March 15th by the National Cancer Institute Current Cancer Blog. A blog first describing Decipher was posted on this website in 2017.

Although the Decipher test was developed nearly a decade ago, the new findings are important because previously there wasn’t enough evidence to recommend its routine use in patient care. Decipher is already available to patients and the cost is covered by many insurance payers, including Medicare. Plus, it doesn’t require an additional procedure if tumor tissue is readily available from the patient’s prostate surgery. There are still many questions about how to use the Decipher test in different groups of patients with prostate cancer. About 20 ongoing clinical studies are looking to provide some answers.

FDA Approves First Oral Hormone Therapy for Advanced Prostate Cancer

On Friday, December 18, 2020, the US FDA approved the first oral gonadotropin-releasing hormone (GnRH) receptor antagonist, relugolix (Orgovyx), for adult patients with advanced prostate cancer. This is an important advance because it offers another option to patients who are taking hormone therapy.

One of the mainstays of treatment for high-risk and metastatic prostate cancer is androgen deprivation therapy (ADT). ADT is designed to stop testosterone from being produced or directly block it from acting on prostate cancer cells, slowing or stopping cancer growth. Most forms of ADT are given as regular injections (e.g., monthly or every 3-4 months) or as implants under the skin. One disadvantage of commonly used medications is an initial spike in testosterone, as well as a delay in time to lowering the man’s testosterone level.

This newly-approved therapy, relugolix, works by blocking the pituitary gland (in the brain) from making hormones that stimulate the testes to make testosterone – thereby lowering a man’s testosterone levels. Instead of an injection, the patient takes an oral tablet once daily, at approximately the same time each day, with or without food.

The effects were tested in a randomized clinical trial comparing relugolix to leuprolide (Lupron), a very common injectable form of ADT, in over 900 patients with advanced prostate cancer. More patients taking relugolix had their testosterone levels fall quickly and remain at a low (“castrate” level) during the study vs those taking leuprolide.

Side effects of ADT can include weight gain, increase in cholesterol levels, and increased risk for heart attack. A striking finding in the clinical trial was a 54% decrease in major cardiac events (such as heart attack and stroke) in the patients taking relugolix vs leuprolide.

What does this approval mean for patients with advanced prostate cancer? They now have an oral alternative to typical ADT that decreases testosterone levels more quickly, and keeps them low, than one commonly used medication. Some patients and doctors may decide that taking an oral medication at home, rather than having to come to the clinic for an injection, may be preferable during the COVID-19 pandemic. Many men with prostate cancer already have risk factors for cardiovascular disease, and relugolix may offer reduced risk of dangerous side effects such as a heart attack. This may be an important consideration when choosing a form of ADT.

For those interested in accessing this medication, the therapy’s developer Myovant Sciences, has launched the Orgovyx Patient Support Program, which will offer patients access to a free trial of the therapy for up to two months, help with verification of insurance plans, copay support for commercially insured patients, and assistance for uninsured patients.

The above was published on December 21st, 2020 by the Prostate Cancer Foundation. For additional information to share with your health provider, see the following link published Jan. 26th, 2021 by the National Cancer Institute in its Cancer Currents Blog.

Long Term Hormone Therapy Raises Risk of Cardiovascular Death

If you have been on hormone therapy (androgen deprivation therapy, ADT) for significant periods of time, e.g. greater than six months, this blog has some valuable information and recommendation for you. A new study reports that long-term exposure to androgen deprivation therapy (ADT), a common treatment for prostate cancer, is associated with worse cardiorespiratory fitness and a higher risk of cardiovascular death. Men who received ADT therapy for more than six months were ultimately found to have a nearly four times higher risk of death than those not exposed to the therapy. The scientists from Brigham and Women’s Hospital and Dana Farber Cancer Institute, both in Boston, noted that further research will be necessary to determine whether cardiovascular-targeted interventions, like exercise, might help reduce cardiovascular risk in prostate cancer patients undergoing long-term ADT. For us with prostate cancer, physical exercise and strengthening are both valuable habits.

For a full article, see the Jan. 11th, 2021 Prostate Cancer News Today.

Study Finds That Provenge Improves Survival in mCRPC Patients Over Xtandi, Zytiga.

Provenge (sipuleucel-T) by Dendreon Pharmaceuticals, is superior to Zytiga (abiraterone acetate) or Xtandi (enzalutamide) at prolonging the lives of men with metastatic castration (hormone)-resistant prostate cancer (mCRPC) when added at any point in a treatment regimen, according to a real-life study in the U.S.

The study, “A Retrospective Observational Analysis of Overall Survival with Sipuleucel-T in Medicare Beneficiaries Treated for Advanced Prostate Cancer,” was published in the journal Advances in Therapy.

“Men with mCRPC who received [Provenge] had a significant improvement in median overall survival and reduction in the risk of death at three years, regardless of line of use,” according to Rana R. McKay, MD, the study’s lead author at the University of California, San Diego.

“This analysis underscores the importance of using complementary mechanisms of action to maximize patient survival outcomes and highlights the critical role immunotherapy plays in the modern era of mCRPC treatment,” said Bruce A. Brown, MD, Dendreon’s chief medical officer. “Provenge continues to deliver on its promise of helping men with advanced prostate cancer live longer and should be considered when making treatment decisions in daily clinical practice,” Brown added.

Approved in the U.S. in 2010, Provenge is the only immunotherapy that uses a patient’s own immune cells to fight prostate cancer. It consists of an individual’s white blood cells that have been exposed to a prostate cancer protein, ultimately priming them to activate the remaining immune cells to fight cancer.

In the years since Provenge’s approval, the oral agents Zytiga and Xtandi — second-generation androgen-receptor signaling pathway inhibitors (ASPIs) — have become the standard-of-care treatment for men with mCRPC. Currently, both ASPIs and Provenge are recommended as a first-line treatment for the same indication. However, no study to date has compared the effectiveness of Provenge with that of the ASPIs. To fill this knowledge gap, Dendreon researchers and colleagues retrospectively analyzed the survival outcomes of 6,044 men with mCRPC who received either Provenge or ASPIs (Zytiga or Xtandi).

The current study explored differences in the survival outcomes, adjusted for multiple factors available in the dataset that could potentially influence the patients’ risk of death.

The results showed that men treated with first-line Provenge lived significantly longer (34.9 months; nearly three years) than those receiving ASPIs as first-line therapy (21 months; just less than two years), reflecting a 44% reduced risk of death at three years. Further, adding Provenge to either Zytiga or Xtandi at any point of the treatment regimen reduced the risk of death by 41% and prolonged median overall survival by 14.5 months (just over one year). Specifically, overall survival was 35.2 months with any-line Provenge versus 20.7 months without the immunotherapy.

These findings highlight that including Provenge at any point during treatment prolongs the life of men with mCRPC by more than one year and reduces their risk of death by more than 40%.

Moreover, exploratory analyses suggested that patients who received both Provenge and an ASPI during their treatments saw their risk of death reduced by 52% compared with only one ASPI or two sequential ASPIs.

“These findings support the need for further research to explore treatment sequences and therapeutic combinations,” the researchers wrote.

For additional details, see the October 26th issue of Prostate Cancer News Today by Marta Figueiredo.

Targeted SBRT Radiation Reduces Pain From Metastases to the Spine

The following Nov. 24th article from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) describes recent clinical trial findings that for some patients with painful spinal metastases from advanced cancer, a type of precise, high-dose radiation therapy (SBRT) may be a highly effective way to relieve that pain. About a third of people in the clinical trial who received this form of radiation therapy, called stereotactic body radiation therapy, or SBRT, for spinal metastases were pain-free up to 6 months after treatment compared with only about 15% of people who received conventional external beam radiation therapy to treat the pain.

This study included about 200 people with three or fewer spinal metastases in a concentrated area of the spine that were the sole source of their pain. None had measurable signs of instability in the bones of the spine, which would increase the risk of fracture and make it harder to assess pain.

The study’s principal investigator noted that “this isn’t for the patient who has pain everywhere in the spine, which is unfortunately the majority of patients. But if you have a defined region of metastatic disease in the spine, and you can pinpoint the pain to that region, that’s going to be who benefits.” See the entire article for details.

With Two New FDA Approvals, Prostate Cancer Treatment Enters the PARP Era.

Two recent approvals by the Food and Drug Administration (FDA) have opened a new avenue of treatment for some men with prostate cancer: an expanded role for targeted therapies.

The approvals are for the drugs olaparib (Lynparza) and rucaparib (Rubraca). They cover the use of the drugs in men whose prostate cancer has spread, or metastasized, and whose disease has stopped responding to standard hormone treatments, often called castration-resistant disease. To receive either drug, men must also have specific genetic alterations that prevent their cells from repairing damage to their DNA.

Many treatments of metastatic prostate cancer are centered around therapies that block the ability of hormones to fuel the cancer’s growth and spread. But olaparib and rucaparib, which are taken as pills, work differently. They block the activity of a protein known as PARP, which helps cells mend specific types of damage to DNA. PARP inhibitors work in part by blocking the ability of PARP proteins to repair damaged DNA, which includes recruiting other DNA repair proteins.

Studies have shown that 20%–30% of men with metastatic prostate cancer have genetic alterations that impair cells’ DNA repair mechanisms. So, to now have two new approved therapies for these men, and in such rapid succession, “is good news for patients,” said Oliver Sartor, M.D., medical director of the Tulane Cancer Center and a prostate cancer expert. The past decade has seen a boom in new treatments for prostate cancer. But few of them are genomic targeted therapies, those intended to work on cells with specific genetic alterations, which are now commonly used to treat other types of cancer.

PARP: Prime Treatment Target for Prostate Cancer
Over the past decade, olaparib and rucaparib have become important treatments for women with ovarian and breast cancer, in whom genetic alterations that affect DNA repair processes are common. Among the most frequent such alterations are those in the BRCA1 and BRCA2 genes.

It’s no accident that researchers have identified people who have alterations in BRCA genes as ideal candidates for treatment with PARP inhibitors. BRCA proteins and some PARP proteins are both integral components of cells’ response to DNA damage. If that response is already dysfunctional because of BRCA1 or BRCA2 mutations, then researchers reasoned that blocking the activity of PARP proteins could further hamper any chance of repair—akin to punching a hole in a tire that already has a slow leak. If the cancer cells can’t fix the DNA damage, they will die.

Prostate cancer emerged as another strong candidate for PARP inhibitors after studies suggested that alterations in BRCA1 and BRCA2, as well as other genes involved in a cell’s ability to respond to DNA damage, may be present in approximately one-quarter of men with the disease. Other studies linked these genetic changes to an increased risk of prostate cancer, as well as more aggressive disease. Those findings, led to a series of clinical trials of PARP inhibitors in men with metastatic prostate cancer, laying the foundation for the new FDA approvals.

PROFOUND Trial: Most Benefit Seen in Men with BRCA2 Alterations
Olaparib’s approval, announced on May 19, was based on the results of a large clinical trial called PROFOUND. The trial enrolled men with mutations in DNA repair genes and divided them into two cohorts. Cohort A included men with alterations in the BRCA1, BRCA2, or ATM genes, each of which plays an important role in DNA repair. Cohort B included men who had alterations in a group of 12 other genes that have some involvement in repairing DNA.

All of the men in the trial had cancer that had worsened despite treatment with either abiraterone (Zytiga) or enzalutamide (Xtandi), which work in different ways to block hormones in prostate cancer cells. The 387 men in the trial were randomly assigned to either the treatment group, which received olaparib, or the control group, which received either abiraterone or enzalutamide (as selected by each patient’s oncologist).

In cohort A, men treated with olaparib lived more than twice as long without evidence of their cancer getting worse (as measured by standard imaging procedures) than men treated with abiraterone or enzalutamide: a median of 7.4 months versus 3.6 months. The treatment group in cohort A also lived longer overall, with olaparib improving survival by more than 4 months (19.1 months versus 14.7 months). In addition, men treated with olaparib were far more likely to see their tumors shrink (a tumor response) than men treated with one of the other two drugs (33% versus 2%).

Prostate cancer tends to spread to the bones, so reducing the size of those particular tumors can have a meaningful impact on patients, according to the trial’s lead investigator, Maha Hussain, M.D., of Northwestern Medicine. Metastases that are poorly controlled in the bone can be quite painful.

FDA’s approval covers the use of the drug in men with alterations in any of the DNA repair genes analyzed in the trial. But Dr. Sartor, who also was an investigator on the trial, noted that men with alterations in BRCA2 seemed to respond best to the treatment, experiencing the largest improvement in progression-free survival. And these men accounted for about one-third of trial participants. Men with ATM alterations, on the other hand, didn’t do any better than those in the control group.

FDA also simultaneously approved two tests, BRACAnalysis CDx and FoundationOne CDx, for identifying patients with metastatic castration-resistant prostate cancer who have the appropriate genetic alterations to receive olaparib.

TRITON2 Leads to Accelerated Approval for Rucaparib
FDA’s approval for rucaparib, announced on May 15, is slightly different than what was granted to olaparib.

To begin with, it was an accelerated approval. That means the approval was granted based on results from a clinical trial that strongly suggests rucaparib could be beneficial for patients—such as an improvement in progression-free survival—although that level of proof is not yet available. In addition, the approved use is only for men with mutations in BRCA1 or BRCA2 and only for cancer that has progressed despite earlier treatment with both a hormone-blocking treatment as well as chemotherapy.

The approval was based on the results of a 115-patient clinical trial, called TRITON2. Similar to the PROFOUND trial, TRITON2 enrolled men with alterations in a host of DNA repair genes, the largest group of which was those with BRCA2 mutations. All the men in the trial were treated with rucaparib.

According to data presented last year—and similar to what was seen in PROFOUND—men with BRCA2 alterations were most likely to respond to the PARP inhibitor. Of the 62 men with BRCA2 alterations, nearly 45% had a tumor response. And, in more than half of these men, the response lasted for at least 6 months.

Overall, Dr. Karzai said, it does appear that BRCA2 alterations “really do drive the benefit” of PARP inhibitors among men with metastatic prostate cancer. “I think we’re really seeing that in these trials.”

Making Treatment Choices: Olaparib or Rucaparib?
Often, when multiple drugs are approved for the same—or in this case, a very similar—use, the side effects associated with each drug can help doctors decide which therapy is best for each patient. Overall, Dr. Sartor explained, there aren’t notable differences in the types or severity of the side effects caused by olaparib and rucaparib.

And although most patients seem to handle the side effects caused by both drugs relatively well, he continued, they can cause substantial problems, including anemia, severe drops in white blood cell count, nausea, and vomiting. Dr. Karzai also pointed to the risk of myelodysplastic syndrome, a disorder that affects the formation of blood cells in the bone marrow and that has been seen in a very small percentage of patients treated with PARP inhibitors. “These drugs definitely require close monitoring [of patients],” Dr. Sartor said.

One potential advantage of rucaparib over olaparib could be the eventual availability of a blood test, called a liquid biopsy, that can identify men with BRCA1 or BRCA2 alterations (as well as other genetic alterations) who are candidates for the drug. This liquid biopsy, called FoundationOne Liquid CDx, is currently being evaluated by FDA and a decision on its approval is expected soon, according to a spokesperson for Foundation Medicine, which manufactures the test.

One reason that’s important, Dr. Karzai explained, also comes back to the fact that prostate cancer so often spreads to the bones. Because bone metastases are often hard and dense, she said, biopsies of these sites are “notorious for not having enough tissue to do standard genetic sequencing.” In addition to tissue quantity, there are also issues with the type of tissue that comes from the biopsy and its quality. “There a lot of variables that can make it difficult,” she added.

The PROFOUND trial provides a case in point: In nearly one-third of tissue samples collected from more than 4,000 men screened as possible participants for the trial, the genetic test used wasn’t able to determine whether the specific genetic alterations were present in 31% of patients. Even with a liquid biopsy, ensuring the routine testing of patients for the presence of alterations in DNA repair genes will likely be the biggest barrier to oncologists’ adoption of these drugs in everyday patient care, Dr. Sartor believes.

The above was received in a National Cancer Institute (NCI) Post dated June 12th.

New Guidelines for Care of Advanced Prostate Cancer

The American Urological Association (AUA), American Society for Radiation Oncology (ASTRO), and Society of Urologic Oncology (SUO) have released new guidelines for the diagnosis and treatment of advanced prostate cancer, developed by a panel of experts. In addition to their own expertise and experience, panel members assessed data from 264 prostate cancer studies in developing these recommendations for clinical practice.

In total, the panel released 38 individual guidelines, grouped into six overarching themes. These are early evaluation and counseling, recurrence without metastatic disease (local treatment exhausted), metastatic hormone-sensitive cancer, non-metastatic castration-resistant disease, metastatic castration-resistant cancer, and bone health. For the entire July 29th article from Prostate Cancer News Today, see the following link.

Adding Provenge to Xtandi or Zytiga Reduces Risk of Death by 45% in Metastatic Hormone Resistant Prostate Cancer

Data from more than 6,000 Medicare patients showed that adding the immunotherapy Provenge (sipuleucel-T) to a regimen containing the oral agents Zytiga (abiraterone acetate) or Xtandi (enzalutamide) significantly extended the lives of men with metastatic hormone-resistant prostate cancer (mCRPC). The findings were presented in a poster at the recent American Society of Clinical Oncology (ASCO) 2020 Genitourinary Cancers Symposium in San Francisco, California.

Provenge, marketed by Dendreon Pharmaceuticals, is an immunotherapy that uses a patient’s own immune cells to fight prostate cancer. In it, a fraction of white blood cells that have been exposed to a prostate cancer protein are primed to activate the remaining immune cells to fight cancer. Provenge is the only immunotherapy approved in the U.S. (2010) for prostate cancer that is made from a patient’s own immune cells. Since 2010, second-generation androgen receptor inhibitors, like Zytiga and Xtandi, have become the standard care treatment for men with mCRPC. This led researchers at Dendreon to assess the benefits of Provenge when used in combination with these agents. The researchers examined medical and pharmacy claims from 6,853 Medicare mCRPC patients who had not received any prior treatment, which means they had no treatment claims in the prior year.

Results indicated that the use of Provenge significantly extended patients’ lives from 20.7 months to 35.2 months. This 14.5-month increase in overall survival represented a 45% reduction in the risk of death. Notably, the benefits were seen at any point during treatment, with patients receiving Provenge as part of their first-line treatment seeing the same extension in overall survival as those receiving the therapy in later lines. At three years, nearly half (48%) of patients receiving Provenge in any line of treatment were alive, compared to 28% of those receiving only Zytiga or Xtandi without Provenge.

Recent findings from an observational registry study called PROCEED also showed that men with asymptomatic or minimally symptomatic mCRPC derive the same benefits from Provenge as those that had been demonstrated in IMPACT. Men with low prostate specific antigen (PSA) levels at baseline fared particularly well, living nearly four years after receiving Provenge.

This is in line with another study also presented at the ASCO GU Cancers Symposium, demonstrating that Provenge works better in men with early-stage prostate cancer — who likely have lower PSA levels — than in those with mCRPC.

“These real-world data contribute to a growing body of evidence that Provenge continues to deliver on its promise of helping men with advanced prostate cancer live longer,” said Bruce A. Brown, MD, chief medical officer at Dendreon.

Several blogs describing Provenge including my own experience with it have been posted on this website. See the following links from 2017, 2014, and 2011.

A portion of the above was an excerpt from the Feb. 20th Prostate Cancer News Today, by Iqra Mumal. I strongly encourage readers to subscribe to this e mail prostate cancer news service.