Hello, my name is Dr. Tom Beer and I am professor of medicine at the Oregon Health & Science University Knight Cancer Institute. I am reporting live from the American Society of Clinical Oncology annual meeting being held here in Chicago, Illinois. Today, I would like to speak to you about several studies. The first of which is the AFFINITY study. A randomized phase III study of a novel clusterin inhibitor custirsen, plus cabazitaxel and prednisone versus cabazitaxel and prednisone alone as second-line chemotherapy in metastatic castration-resistant prostate cancer. This is a study that is still recruiting participants and is being presented at this meeting as a trials and progress report. In this study, custirsen, the investigational drug, is designed to inhibit clusterin, a protein that is thought to be driving resistance to conventional chemotherapy. The study is designed to determine whether inhibiting clusterin with this investigational agent will lengthen survival of patients receiving cabazitaxel as second-line therapy. The study is underway, still looking for volunteers around the country, and represents I think a novel effort to target a specific resistance mechanism using antisense oligonucleotide technology, which is a way of shutting down the protein at the level of its genetic translation before it is actually manufactured by the cancer cells. This study is underway and we will eagerly await the completion of accrual of the patients and then the analysis of the results.
The next presentation from this meeting that I would like to mention is the long-term safety and efficacy analysis of abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer in patients who have not had prior chemotherapy. This is a study that has been presented at this meeting last year and published in The New England Journal of Medicine. It is really a landmark clinical trial that established the fact that suppressing androgen synthesis with the drug abiraterone can delay the progression of prostate cancer even in patients who have not had chemotherapy before. What we know about this drug today is that in patients who have been through chemotherapy, the drug can delay disease progression and significantly improve overall survival that led to the approval of this drug for the treatment of such patients, and we also know from the trial presented at this meeting that it can delay the disease progression and chemotherapy-naïve patients, and there is a trend in favor of an overall survival advantage in that setting as well. The difficulty in measuring survival in prechemotherapy studies is that patients following treatment on the clinical trial have the opportunity to be treated with many agents that can also modulate survival. That is obviously great news for patients, but it is a difficulty for studies because the survival impact of a treatment can be deluded by subsequent therapy including crossover to the investigational agent itself which is currently available in the market. What is important about the presentation from that trial at this meeting is the long-term safety data. For some patients this drug can be very effective and patients are staying on the drug as long as for several years and what Dr. Rathkopf and her collaborators reported at this study is that there is no unexpected toxicity signal from long-term exposure, so we are not seeing late toxicities emerge that might be important for those patients who are benefiting from the drug and need to stay on it for a long time.
The next trial I wanted to mention is another trials and progress report entitled “A randomized, double-blind phase III trial to compare the efficacy of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naïve castration-resistant prostate cancer.” This is another trials and progress report, so what was discussed at this meeting is the design and rationale for the study. The results are obviously eagerly awaited. I think this trial represents a very exciting avenue for investigation in several ways. First of all, sipuleucel-T is the first immunologic therapy approved for prostate cancer and has been shown in a randomized study to extend survival. So we know that targeting the immune system can be effective and that gives us an entirely new avenue for investigation with a variety of novel agents. Ipilimumab takes a different approach than sipuleucel-T. It blocks one of the mechanisms of tolerance, basically activating the immune system and giving it a second opportunity to recognize prostate cancer as something that deserves, if you will, attention from the immune system. Ipilimumab has been shown to significantly improve survival in melanoma. We, together with a number of collaborators around the country, published results from phase I/II study that showed that this drug, simply by activating the immune system, can lead to responses in patients with advanced prostate cancer, and the phase III trial that is being discussed at this meeting is seeking to determine whether that can translate into an overall survival advantage. This trial has completed accrual of its participants and we are waiting for the results to mature so that we can determine if this drug produces meaningful patient benefits.
The last report is one from our group that I am very excited about entitled, “Open-label, multicenter study of sipuleucel-T in men with metastatic castration-resistant prostate cancer previously treated with sipuleucel-T: evaluation of antigen-presenting cell activation and ELISPOT data.” Now, this is a report where we actually have results. It is not a trials in progress report, and it is fairly unique. The study examined the ability of sipuleucel-T to durably stimulate the immune system, so participants in this study had previously been treated with sipuleucel-T on average 8 years ago on the so-called P11 trial, and in this new study were re-enrolled to measure their immune activation before starting any additional therapy and then received another round of sipuleucel-T. Through a variety of measures of immune response what where we are able to demonstrate in this study is that there appears to be long-term immune memory induced by sipuleucel-T and retreatment is both feasible and safe and results in actually greater activation of the immune system than we see after initial therapy. It is too early to recommend this approach in routine clinical care. This is a preliminary study, but it is certainly encouraging to see both the evidence that the immune activation is lasting for many, many years and the fact that retreatment can boost it further. So, I think we will see in the future studies emerging from this work looking at the possibility that booster rounds of sipuleucel-T therapy may improve the outcomes for patients undergoing this type of immunologic therapy. So, thank you very much for your attention and I appreciate the chance to bring you up-to-date on some of the exciting presentations here at the 2013 ASCO meeting.
Design of the AFFINITY study: A randomized phase III study of a novel clusterin inhibitor, custirsen, plus cabazitaxel/prednisone (CbzP) versus CbzP alone as second-line chemotherapy in metastatic castration-resistant prostate cancer (mCRPC). http://meetinglibrary.asco.org/content/115329-132
Long-term safety and efficacy analysis of abiraterone acetate (AA) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy (COU-AA-302).http://meetinglibrary.asco.org/content/111574-132
CA184-095: A randomized, double-blind, phase III trial to compare the efficacy of ipilimumab (Ipi) versus placebo in asymptomatic or minimally symptomatic patients (pts) with metastatic chemotherapy-naive castration-resistant prostate cancer (CRPC). http://meetinglibrary.asco.org/content/109912-132
ASCO 2013 - Poster: Open-label, multicenter study of sipuleucel-T in men with metastatic castrate resistant prostate cancer (mCRPC) previously treated with sipuleucel-T: Evaluation of antigen presenting cell (APC) activation and ELISPOT data