Malecare and the University of Minnesota, with funding from the National Cancer Institute at NIH, are collaborating on an exciting new study. The RESTORE study, http://z.umn.edu/restorestudy
looks at how prostate cancer treatment affects gay and bisexual men, our life and sexual partners, and our family and friends who provide care for us during treatment. Guys who have had treatment and their partners are eligible
As a thank you, all participants will receive a $50 Amazon gift card for a 60-90 minute telephone interview. Click here to participate http://z.umn.edu/restorestudy
One focus of this study is to see how different types of treatment affect sexual functioning and gay relationships. The researchers need this information to design better treatments for the sexual and relationship effects of prostate cancer treatment, which may indeed apply to all men, gay and straight. Please consider participating! And, did we mention there is a $50 Amazon gift card for you? You can sign up by phone at 1-844-262-9845 or email: email@example.com
Increasingly there is more and more evidence that a blood test that is used to measures the number of cells circulating in the blood and shed from prostate tumors into the bloodstream (circulating tumor cells or CTCs) can act as an early warning sign that a treatment is not working.
In a major new study researchers showed that measuring the numbers of these circulating tumor cells in the blood predicted which if a man was benefitting from a prostate cancer treatment after beginning the treatment in as little as 12 weeks.
As tumors grow and progress, they shed some of their cells into the bloodstream, some of which can probably seed new metastases. So the researchers wanted to see whether a high number of circulating tumors cells was an indication of a growing tumor that wasn’t responding to treatment, and could predict a lower chance of survival.
Using circulating tumor cells to verify is a treatment is effective should allow doctors to switch men to an alternative treatment earlier than is currently possible. These results do need some more confirmation by further studies. Anther hidden possible benefit of using CTCs is that it might hasten the development of additional new treatments by speeding up clinical trials by using CTCs as surrogate biomarkers.
This study involved the detailed analysis of blood samples from 711 men who took part in a major phase III trial of the prostate cancer drug abiraterone.
The researchers measured numbers of circulating tumor cells at four-week periods after the start of treatment with the drug, along with a range of other biomarker molecules in the blood including lactate dehydrogenase (LDH), high levels of which are a sign of general tissue damage.
The trial itself had used the standard trial end points of average overall survival and survival free of cancer progression to show abiraterone’s (Zytiga) effectiveness in late-stage prostate cancer. But the researchers were able to cross-reference those results with data on circulating tumor cells and LDH levels in each man taking part.
They found a correlation between those men who had responded least well to treatment with abiraterone, and higher levels of cancer cells and LDH in the bloodstream, measured 12 weeks after starting treatment. They showed that levels of circulating tumor cells varied independently of a range of other biomarkers.
To prove the effectiveness of a new drug, clinical trials normally need to be run until the cancer is progressing clinically for each patient – and often until many of the patients on the trial have died. By using CTCs it might be possible shorten the time of clinical trials as well as shorten thr time we keep men on a treatment that is not effective.
H. I. Scher, G. Heller, A. Molina, G. Attard, D. C. Danila, X. Jia, W. Peng, S. K. Sandhu, D. Olmos, R. Riisnaes, R. McCormack, T. Burzykowski, T. Kheoh, M. Fleisher, M. Buyse, J. S. de Bono. Circulating Tumor Cell Biomarker Panel As an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer. Journal of Clinical Oncology, 2015; DOI:10.1200/JCO.2014.55.3487
Joel T. Nowak, M.A., M.S.W.
Immunotherapy has a major and expanding role in the treatment of cancer, including advanced prostate cancer. Over time there have been a number of naysayers as the immunotherapy Provenge has played the role whipping boy by critics. The common criticism leveled at Provenge can be summed up simply, “It doesn’t work.”
The plain truth is that this criticism is not true. Provenge does extend life, but it does not affect a man’s PSA nor does it affect radiologic progression. However, it does extend life, the most important factor for us with advanced prostate cancer.
Why is Provenge (and immunotherapy) not provided it proper acknowledgment? It is money. Provenge consists of three separate treatments at a total cost that is in excess of $105,000. From a statistical analysis you could say that each month of additional survival costs (4.1 months based on the IMPACT Trial) approximately $25,000.
Each of us needs to decide the morality of this price tag, but newer immunotherapies are performing better (longer survival extension) at hopefully will come to market at a cheaper cost. Ipilimumab (Yervoy) has been approved for the treatment of metastatic Melanoma and Prostvac is in the middle of its phase 3 trials (phase 1 and 2 trials all demonstrated a significant survival advantage) for men with advanced prostate cancer.
It is now time for the naysayers to drop the anti-immunotherapy attitude. It extends life and does it with out many of the extreme side effects we experience from both the hormonal therapies as well as the toxic chemotherapies. Evidence strongly suggests that immunotherapy will play an important role in treating prostate cancer as well as many other cancers.
Preliminary results have shown that Prostvac vaccine with ipilimumab ¬(Yervoy) boosts overall survival in men with castration-resistant prostate cancer.(1)
Two previous phase II trials looked at Provenge alone and found an overall survival benefit in men with metastatic castration-resistant prostate cancer. The first trial, which included 125 men, found a median overall survival of 25.1 months. The second trial, which included 32 men, showed a median overall survival of 26.6 months. Both trials demonstrated improved overall survival over that predicted by the Halabi nomogram (a model that uses historical data to estimate survival of prostate cancer patients after castration): The first study showed an 8.5-month improvement in median overall survival, and the second had a similar 9.1-month improvement in median overall survival compared with predicted survival.
At the recent ASCO GU meeting there was additional data presented on a phase 1 trial of 30 men with metastatic castration-resistant prostate cancer (and baseline characteristics similar to those in the phase II trials) treated with the combination of Prostvac plus escalating doses of ipilimumab. Follow-up was about 80 months.
The predicted survival of chemotherapy-naive patients with metastatic castration-resistant prostate cancer is 18.5 months on the Halabi nomogram. The updated overall survival analysis showed a median overall survival of 31.3 months using the intensified immunotherapy approach.
The most impressive results were seen in the group receiving the highest dose of ipilimumab (10 mg/kg) plus the vaccine: a median overall survival of 37.2 months. Additionally, it was disclosed that there is a major tail in the survival curve of this trial. About 20% of the men on the highest dose of ipilimumab are still alive at 80 months.
It is time for all of us to acknowledge the future role of immunotherapy in the treatment of advanced prostate cancer. We all owe a major debt to Provenge as it opened the possibility of using immunotherapy to successful extend our life.
1. Singh H, Madan RA, Dahut WL, et al: Combining active immunotherapy and immune checkpoint inhibitors in prostate cancer. 2015 Genitourinary Cancers Symposium. Abstract 172. Presented February 26, 2015.
Joel T Nowak, M.A., M.S.W.
One of the more difficult problems faced by some men treated with surgery as their primary treatment modality is post-prostatectomy incontinence (PPI). PPI can affect the quality of life for both men successfully treated as well as those who go on and eventually develop advanced prostate cancer.
One of the more common, but last efforts to help a man to regain a level of continence is by having a “male sling” installed. One of the more common slings is known as the AdVance Sling.
In an attempt to evaluate the patient perceived efficacy of the AdVance Sling researchers performed a three (3) year follow-up of men using the sling with post-prostatectomy incontinence (PPI).
The researchers prospectively collected data from men with PPI treated with the AdVance male sling between February 2008 and March 2010. They looked at the twenty-four-hour pad counts and weights as well as patient completed validated questionnaires that were filled out prior to the installation of the sling and at 3 years post installation.
The researchers used as their primary outcome an improvement in pad count with secondary outcomes of questionnaire scores and patient perception of success.
At a follow-up of 39 months the researchers were able to identify 30 men meeting the inclusion criteria who had the AdVance male sling placed for mild to severe PPI.
1- Eighteen (60%) of the men a major success with no pad usage or one pad for security.
2- Four (4) men (13%) showed improvement with a greater than or equal to 50% reduction in their pad usage.
3- Eight (27%) men failed having not received any resolution or improvement in their PPI.
The AdVanc Male Sling does provide an effective treatment option for men with PPI post surgery and should be considered as a possible solution to this problem.
Neurourology and Urodynamics; The Advance Transobturator Male Sling for Post-Prostatectomy Incontinence: Subjective and Objective Outcomes With 3 Years Follow Up; Neurourol Urodyn 2015 Mar 01;34(3)251-254, CG Kowalik, JM DeLong, AP Mourtzinos
Joel T Nowak, M.A., M.S.W.
Before I get into the meat of today’s post about enzalutamide, I want to briefly make some personal comments about my absence from this blog. As I had mentioned I have been diagnosed with a fifth primary cancer, appendiceal cancer. It is a rare cancer, which required my having to remove my appendix, a piece of my right colon, have an exploratory of my entire peritoneal sack and then what is called HIPEC chemotherapy. The surgery and chemotherapy were rough and came with an extended recovery. I am now at the point in my recovery that I am feeling able to again post to the blog as well as pick up my other Malecare responsibilities. I hope to again continue regular updates. I missed everyone and am very glad to return.
Now to the important work, TODAY’S POST:
Medivation, Inc. and Astellas Pharma Inc. today announced additional data from their Phase 2 TERRAIN trial of enzalutamide (Xtandi) compared to bicalutamide (Casodex) in metastatic castration-resistant prostate cancer (mCRPC), as well as an updated overall survival analysis from the placebo-controlled Phase 3 PREVAIL trial of enzalutamide in chemotherapy-naive metastatic CRPC.
The data from these two trials was presented during a plenary session at the 2015 European Association of Urology (EAU) Congress in Madrid.
The data from the phase 2 TERRAIN trial derived from 375 men with castrate resistant prostate cancer from both North America and Europe. All men had metastatic prostate cancer whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue (Lupron, Zoladex, etc.) therapy or following surgical castration.
The primary endpoint of the trial was progression-free survival (PFS) as confirmed by radiographic progression, a skeletal-related event, initiation of new anti-neoplastic therapy or by the subject’s death.
The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once daily versus bicalutamide at a dose of 50 mg taken once daily, the FDA approved dose in combination with an LHRH analogue.
The study achieved its primary objective of a statistically significant increase in PFS for enzalutamide compared to bicalutamide. The median PFS in the enzalutamide arm was 9.9 months longer compared to that in the bicalutamide arm (15.7 vs. 5.8 months, respectively).
The median time to PSA progression was 13.6 months longer with enzalutamide (19.4 months) relative to bicalutamide treatment (5.8 months).
Eighty two percent (82%) of enzalutamide-treated men achieved = 50% PSA reduction from baseline by week 13 vs. 21% of bicalutamide-treated men.
The median time on enzalutamide treatment was 11.7 months compared to 5.8 months on bicalutamide.
Also released was additional data from the important Phase 3 PREVAIL trial which was a randomized, double-blind, placebo-controlled, multi-national trial, enrolling 1,717 men from the United States, Canada, Europe, Australia, Russia, Israel and Asia.
This trial enrolled men who were chemotherapy-naïve (not yet had chemotherapy) who also had metastatic prostate cancer whose disease progressed on androgen deprivation therapy (i.e., a LHRH therapy or after bilateral orchiectomy) (mCRPC). This trial provided the FDA the data that led to the approval of enzalutamide at the pre-chemotherapy stage of the disease.
The co-primary endpoints of this trial were overall survival (OS) and radiographic PFS. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once daily versus placebo.
An updated overall survival analysis was conducted at 784 deaths and found a statistically significant overall survival benefit with a 23% reduction in risk of death and a 4-month improvement in median survival with enzalutamide (35.3 months [95% CI 32.2 – not yet reached]) over placebo (31.3 months [95% CI 28.8 – 34.2]).
As of the June 2014 cut-off date of the trial with a median follow-up duration of 31 months: fifty two percent (52%) of the men receiving enzalutamide and eighty one percent (81%) of men receiving a placebo received one (1) subsequent life-extending prostate cancer therapy.
According to Bertrand Tombal, M.D., Ph.D., professor and chairman, Department of Urology, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium, “This study demonstrates that starting patients on enzalutamide at the point when their castration-resistant prostate cancer becomes metastatic has the potential to prolong survival.”
Both of these additional data points confirm that over both placebo and bicalutamide enzalutamide is superior. What this data doesn’t tell us is how enzalutamide would perform under the following circumstances:
1- How it compares to using Abiraterone (Zytiga).
2- How it compares to using it earlier (in the castrate sensitive man) along with other hormone therapies or alone.
3- How it compares with combining it with Abiraterone.
4- How the dose of bicalutamide of 150mg as is commonly used in the UK would hold up against enzalutamide.
It is good news that these data continue to support the use of enzalutamide (Xtandi), but we call on Medivation and Astellas to expand their research to answer the above-mentioned concerns.
Joel T Nowak, M.A., M.S.W.