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

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.

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.

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

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

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

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.