In this podcast, we review some of the news announced at the 2014 Genitourinary Cancers Symposium, co-sponsored by ASCO.
ASCO: You're listening to a podcast from Lineagotica. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors that care for people with cancer.
In today's podcast, we'll review some of the news announced at the 2014 Genitourinary Cancer Symposium cosponsored by ASCO. This podcast will be lead by Dr. Charles Ryan, who is an associate professor of medicine in the division of Hematology-Oncology at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. Dr. Ryan is also a member of ASCO's Cancer Communications Committee. The symposium, held January 30th through February 1st, 2014, in San Francisco, California, offers presentations on the latest multidisciplinary research for genitourinary cancers. Specifically, the highlighted research includes news about prostate and kidney cancer in addition to news about genitourinary clinical trials that end early.
This Lineagotica podcast helps put new research findings into context and explains what this news means for patients. ASCO would like to thank Dr. Ryan for summarizing these findings.
Dr. Ryan: Hello. My name is Charles Ryan. I'm a medical oncologist at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco. I'm going to be reviewing four of the abstracts that are presented in the presscasts at the ASCO Genitourinary Cancer Symposium, which will be held in San Francisco on January 29th through 30th of 2014.
The first abstract is presented by Dr. Fossa, from Oslo University in Norway and it relates to 10 and 15-year prostate cancer-specific survival in patients who have high-risk prostate cancer, who were randomized to receive hormone treatment alone, or hormone treatment combined with radiation therapy. Now, previously, these data have been presented. This is an update with a longer duration of follow-up, and more mature data. Briefly, this trial was conducted between 1996 and 2002 with 875 patients, who were randomly selected to receive hormonal therapy alone or hormonal therapy with radiation therapy to the prostate. The current results demonstrate that there were 118 deaths from prostate cancer of the 439 patients who were treated with hormonal therapy alone, and there were only 45 deaths out of the 436 men who were treated with a combination of radiation therapy and hormonal therapy. This is a highly statistically significant result.
And actually, when one looks at death from any cause, even death not related to prostate cancer, there was an advantage for those patients who had received the radiation therapy. So in other words, these results show that the 10- and 15-year cumulative prostate cancer-specific mortality is cut in half—it's actually cut in more than half—with the combination of treatment that included radiation therapy. This is a highly statistically significant result and, again, supports the earlier data that was presented, and I think is actually very supportive of the use of a local treatment such as radiation therapy in patients with high-risk, non-metastatic prostate cancer. We don't know if these data can be utilized in other settings such as, for example, patients who do have metastatic prostate cancer or prostate cancer that has spread from the prostate to other parts of the body. We also don't know if these data would be useful if patients had undergone surgery rather than radiation, that surgery being to remove the prostate. Nevertheless, although these questions remain unanswered, it's a very provocative result and supports our use of radiation therapy in these patients.
The next abstract is entitled Premature Termination of Genitourinary Cancer Clinical Trials, and it's presented by Stensland and colleagues, who represents investigators from a variety of institutions, most notably, Mount Sinai in New York. This is a very interesting study in which the investigators explored, over a six-year period, clinical trials in genitourinary cancers. This included prostate cancer, kidney cancer, bladder cancer, and testicular cancer. And they explored how many of these trials actually finished according to the planned accrual and/or were terminated early for one reason or another. As it turns out, 25% of all the trials opened in that period at a variety of institutions that were registered through clinicaltrials.gov, which is the National Cancer Institute's registry forum for such trials, 25% of the trials discontinued prematurely. They go on to describe why this occurred or what were the reasons for termination of these trials. The vast majority of them—or I should say the most common reason for termination was poor accrual, meaning the study was not finding enough patients who met the eligibility criteria in order to finish on time. And many cancer centers will terminate a trial that is not accruing at a rapid rate. Other reasons included lack of funding or toxicity of the drug, or other reasons. Interestingly, clinical trials in cancer were only terminated for toxicity or adverse events related to the therapy in 8% of the settings.
So it is not that common for trials to be terminated because of toxicity of the drug. While this data is very preliminary and quite interesting, it is very important to those of us who design and conduct clinical trials in genitourinary cancers because it gives us a glimpse as to what types of threats there are that face these trials. And it gives us information that might help us to design trials more effectively. So while these data may not immediately change patient practice, they will certainly be integrated into the thinking of those of us who design these clinical trials.
The next abstract comes from McKay and colleagues from the Dana-Farber Cancer Institute in Boston and looks at the impact of angiotensin system inhibitors, which are a class of drugs used to treat hypertension, on outcome in patients with metastatic renal cell carcinoma. There are two classes of drugs that are considered angiotensin system inhibitors. ACE inhibitors, as they're commonly used, or angiotensin receptor blockers. And both of these are very commonly used medicines by primary care physicians to treat hypertension. And as a result, many patients who have kidney cancer may also be treated with these either as a result of pre-existing hypertension or potentially due to hypertension related to the therapy that they receive. The interesting aspect of these agents is they may alter blood flow to the kidney and that that may alter the outcomes of patients with kidney cancer. In this investigation, the researchers identified 4,736 patients who were treated with various different medical treatments for kidney cancer.
Now all of these treatments—or many of these treatments, I should say—were agents that do affect blood pressure and may increase blood pressure. When the investigators looked at the use of the angiotensin system inhibitors and reported the progression-free survival, or the duration of time that the therapies were useful for patients, as well as the overall survival or the length of survival of these patients, it was determined that both the time to the disease progression or the progression-free survival, as well as the overall survival of patients, was increased in the patients who were using these drugs. There were 1,383 of these patients who were using the drugs, and 3,353 patients who were not. As the numbers demonstrate, there was a very significant improvement in survival. 25.6 months was the average survival of the patients who were using this type of drug, and 17.3 months was the average survival in the patients who were not. This was associated with about a 26% improvement in survival by the use of these antihypertensive drugs. This is a highly statistically significant result. However, one needs to be cautious in interpreting these because this is a retrospective study. And so when we look at retrospective data, we have not controlled for all possible variables like we do when we do a clinical trial. And therefore it's possible that there are other factors that may be associated with the differences in outcomes, other than the use of these drugs. Nevertheless, I think it is a provocative finding, and it does demonstrate that these therapies may improve the survival in these patients, and that further study is certainly required in this approach. And we will look for further research from this group on this very question.
The next abstract is a late-breaking abstract entitled Enzalutamide in Men with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer. These are the results of a phase III study, which is called the PREVAIL Study. And the first author on this is Dr. Tomasz Beer from Oregon Health Sciences University. This was a very important clinical trial. This was for men with chemotherapy-naive metastatic castration-resistant prostate cancer, which really constitutes the largest group of patients who are present now in the world with castration-resistant prostate cancer. And it tests enzalutamide, which is an FDA-approved drug, an orally available treatment, that blocks androgen receptor signaling. So it blocks hormonal signaling in prostate cancer. The trial enrolled 1,700 men between September of 2010 and September of 2012. What we are seeing here are the data reported from an interim analysis. An interim analysis is done, as the name implies, before all of the data have been finalized. So many of the patients who have been enrolled in this trial are not only still alive, but may also still be receiving the treatment. The interim analysis that was done showed a benefit of enzalutamide over placebo with a 30% risk reduction in deaths and an 81% reduction in the risk of progression. So in this trial, patients were randomly selected to receive enzalutamide once daily or a placebo.
And these results are strongly positive for both of the primary endpoints of progression-free survival and overall survival. There are a couple of very encouraging signs coming from this trial. I think it is very exciting that this is a potentially new standard of care in this chemotherapy-naive patient population. A couple of interesting points to note, however, is that this is an interim analysis, and only 28% of the patients who had enrolled into this trial have died. And one of the main endpoints is to look at how long people are surviving. So 72% of the patients, we don't know what their long-term outcome is yet. So in other words, this is still an early result and it may change over time. It is unlikely to become a negative trial, but the actual numbers may change and the actual benefit may change over time as well. The other interesting aspect is that the estimated median overall survival in this trial was 32.4 months in the enzalutamide arm and 30.2 months in the placebo arm. Now, while that looks like it's a very statistically significant result based on the numbers enrolled in the trial, the actual difference in survival was not that significant in terms of the duration of time. It is also shorter than the median survival of a similar study done with a similar drug, abiraterone, which was reported earlier. So this may evolve over time and may change, but it does demonstrate a very positive result for this therapy. And we will be looking at how this gets integrated into clinical care with enthusiasm.
ASCO: Thank you, Dr. Ryan. More news from the 2014 Genitourinary Cancers Symposium can be found at lineagotica.info.
Lineagotica is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding breakthrough research, sharing knowledge with physicians and patients worldwide, and supporting initiatives that ensure that all people have access to high-quality cancer care. Thank you for listening to this Lineagotica podcast.