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6th Annual Interdisciplinary Prostate Cancer Congress Integrating New Therapies into the Prostate Cancer Continuum Resources

6th Annual Interdisciplinary Prostate Cancer Congress™ Integrating New Therapies into the Prostate Cancer Continuum


Community Practice Connections: 6th Annual Interdisciplinary Prostate Cancer Congress™
Earn up to 0.75 AMA PRA Category 1 Credits™
Drs Dreicer, Gomella, and Petrylak address a variety of questions commonly faced in the community oncology practice setting.

6th Annual Interdisciplinary Prostate Cancer Congress™: Meeting-in-a-Box

PER Pulse™ Recap

PER Meeting in a Box

6th Annual Interdisciplinary Prostate Cancer Congress™: Meeting-in-a-Box

The Meeting-in-a-Box components below are designed for you to download and share the information with colleagues, fellows, and other health care professionals.

Included in the Meeting-in-a-Box:

PER Pulse™ Recap

PER Pulse™ Recap

Three PER Pulse™ Recaps presenting key topics from the 6th Annual Interdisciplinary Prostate Cancer Congress™, which was held on March 16, 2013.

Medical Writer: Jennifer Klem, PhD

1 of 3
6th Annual Interdisciplinary Prostate Cancer Congress™
PSA Screening and Active Surveillance

On March 16, 2013, the 6th Annual Interdisciplinary Prostate Cancer Congress™ was held to discuss and debate the cutting-edge management of men with prostate cancer. This PER Pulse™ Recap is the first of three presenting key topics from the 6th Annual Interdisciplinary Prostate Cancer Congress™, specifically, the controversial topics of PSA screening and active surveillance:
  • Dr. Leonard Gomella undertook the task of presenting the debate surrounding PSA screening. In 2012, the US Preventive Services Task Force published a recommendation statement against PSA screening for any asymptomatic man, suggesting that there is likely no net benefit of screening for prostate cancer. This creates a scenario in which many insurance carriers will not reimburse screening costs for asymptomatic men. Prospective PSA screening clinical trials have produced conflicting results, with one showing no survival benefit but two others reporting a reduction in mortality. However, certain analyses of these trials (ie, removing patients with comorbidities, using longer follow-up) provide a more consistent and favorable picture of PSA screening benefit. The dramatic increase in 10-year prostate cancer relative survival rate since 1975 (from 53.5% to 97.2%) has likely been the result of both improved treatments and increased screenings.

    Based on these data, Dr. Gomella concluded that PSA screening is not beneficial for the general population, but it does benefit those men at high risk for prostate cancer who are in good health and have a life expectancy of at least 10-15 years. He advocated for screening these men, but cautioned against overtreatment by considering active surveillance rather than active treatment in many of these PSA screening-detected cases of prostate cancer.
  • Dr. David Crawford provided an in-depth examination of active surveillance, defining it as a means to provide early, curative treatment for localized disease, in contrast to watchful waiting, which aims to delay the palliative treatment of someone with advanced disease. The increasing interest in active surveillance in recent years is due to a number of factors, including a greater recognition of the issue of overtreatment, a better understanding of occult high-grade disease, new surveillance techniques (multiparametric MRI, staging biopsies), and a better grasp of the flaws of tracking disease progression using PSA kinetics. Active surveillance also delays or avoids quality-of-life declines caused by active treatment, such as sexual dysfunction and urinary incontinence caused by radical prostatectomy or radiation therapy.

    The PIVOT trial conducted within the VA hospital system demonstrated that survival of patients receiving radical prostatectomy was not improved compared with those receiving observation only, particularly in those patients with low-risk disease. The National Comprehensive Cancer Network recommends active surveillance as the preferred management approach for men with a very low risk of recurrence when life expectancy is <20 years and as one of three reasonable management options for those at low risk of recurrence when life expectancy is <10 years. A number of different follow-up schedules and monitoring techniques (ie, PSA cut-off value, PSA kinetics, Gleason score progression, clinical progression) have been advocated by various groups.

    Dr. Crawford recommended that active surveillance should be offered to men with Gleason scores of 6 and PSA ≤ 10 ng/mL, and suggested that a confirmatory biopsy be performed within 1 year and repeat biopsies performed every 3-5 years up to age 80. He emphasized that patients who are appropriately chosen for active surveillance generally do well.
Click here to download PDF version

2 of 3
6th Annual Interdisciplinary Prostate Cancer Congress™
Endocrine and Chemotherapy Options

At the 6th Annual Interdisciplinary Prostate Cancer Congress™ held on March 16, 2013, systemic treatment options for patients with castration-resistant prostate cancer (CRPC) were among the key topics discussed. This PER Pulse™ Recap, the second of three recaps from the 6th Annual Interdisciplinary Prostate Cancer Congress™, reviews highlights from lectures focused on endocrine and chemotherapy options for advanced prostate cancer:
  • Dr. Daniel Petrylak reviewed data on chemotherapy regimens for men with metastatic CRPC. Currently, two chemotherapy agents have demonstrated a survival advantage compared with the palliative regimen of mitoxantrone plus prednisone for the treatment of mCRPC: docetaxel in the first line and cabazitaxel in the second line. A number of biologic agents (bevacizumab, aflibercept, lenalidomide, atrasentan, dasatinib, and others) have been added to docetaxel in an attempt to improve patient outcomes, but these trials have all failed to improve overall survival. There is another ongoing phase III trial of a combination docetaxel regimen: the SYNERGY trial comparing docetaxel with or without custirsen, an antisense oligonucleotide directed against the antiapoptotic clusterin molecule. This trial, which was initiated after a randomized phase II trial showed a possible survival advantage with this combination, is scheduled for completion by the end of 2013. Other ongoing randomized chemotherapy studies include docetaxel versus cabazitaxel in the first line, and lower-dose cabazitaxel versus standard-dose cabazitaxel to try to improve its safety profile. In addition, the use of biomarkers, both to predict response to therapy and to aid in rational drug development, is also being explored.
  • Dr. Robert Dreicer discussed the exciting topic of new endocrine options for advanced prostate cancer, focusing on the two recently approved hormonal therapies for the treatment of mCRPC: abiraterone and enzalutamide. The lyase inhibitor abiraterone was approved by the US Food and Drug Administration (FDA) in 2011 for the treatment of patients with mCRPC after treatment with docetaxel, on the basis of a 3.9-month improvement in survival over placebo. As long as abiraterone is given in combination with low-dose steroids to minimize mineralocorticoid-related toxicity, it is a well-tolerated therapy. The antiandrogen enzalutamide was approved for mCRPC after demonstrating a 4.8-month survival advantage over placebo in patients previously treated with docetaxel. It is also well tolerated, and it has no need for steroid replacement.

    Given the success of these agents in the post-chemotherapy setting, they are also being examined for their use earlier in the disease course of prostate cancer. Abiraterone has already earned an expanded indication as first-line therapy for chemotherapy-naïve mCRPC after demonstrating a 25% reduction in the risk of death compared with prednisone alone. Enzalutamide is currently in phase III testing in chemotherapy-naïve mCRPC, and results should become available sometime in 2013. Questions that remain to be answered concerning the optimal integration of endocrine therapies into the management of CRPC include the timing of drug administration, the role of combination therapy, the feasibility of discontinuing androgen biosynthesis inhibitors, the optimal dose of steroid support for abiraterone, and the prediction of response to endocrine therapy.
Click here to download PDF version

3 of 3
6th Annual Interdisciplinary Prostate Cancer Congress™
Immunotherapies and Bone-Targeted Therapies

The 6th Annual Interdisciplinary Prostate Cancer Congress™, held on March 16, 2013, discussed state of the art treatments for men with prostate cancer. This is the third of 3 PER Pulse™ Recaps covering important topics from the 6th Annual Interdisciplinary Prostate Cancer Congress™, and in it, we review highlights from the presentations on bone-targeted therapies and immunotherapies:
  • Dr. Daniel Petrylak reviewed data on existing and novel bone-targeted therapies for men with metastatic castration-resistant prostate cancer (mCRPC). Currently, there are several bone-targeted therapies approved by the US Food and Drug Administration (FDA), including the bisphosphonate zoledronic acid and the RANK ligand inhibitor denosumab. When these 2 agents were compared in a phase III trial, denosumab proved superior in time to first on-study SRE (skeletal-related event; 20.7 months vs 17.1 months; P = .008) but it also was associated with a slight increase in osteonecrosis of the jaw (2.3% vs 1.3%; P = .09). Two beta-emitting radioisotopes, samarium-153 and strontium-89, have also earned FDA approval on the basis of significant improvements in pain and decreases in analgesic use.

    There are also several promising new bone-targeted therapies on the horizon for mCRPC. The first is the alpha-emitting radioisotope radium-223. Alpha particles have a shorter penetration range compared with beta particles, but induce double-stranded DNA breaks, a combination that may potentially improve efficacy while decreasing damage to normal tissues. In the phase III placebo-controlled ALSYMPCA trial in symptomatic patients with CRPC and bone-only metastases who had previously received or were unfit for/refused docetaxel, radium-223 improved overall survival by 3.6 months (HR = 0.695; P = .00007) and delayed time to first SRE by 5.5 months (HR = 0.64; P <.0001). Safety data were favorable, with the radium-223 group showing no increases in overall, grade 3/4, or serious adverse events (AEs), in discontinuations due to AEs, or in deaths due to AEs. Neutropenia, thrombocytopenia, and diarrhea appeared slightly more frequent in the radium-223 group. This agent was approved by the FDA on May 15, 2013 for use in CRPC with symptomatic bone metastases and no known visceral metastases. Another novel agent, the small molecule VEGFR2/MET inhibitor cabozantinib (XL184), has also shown promise in mCRPC in a 93-patient study, not only improving bone scans and pain scores, but also producing regression of soft tissue disease.
  • Dr. Susan Slovin provided an overview of immunotherapies under investigation for the treatment of CRPC, discussing not only data from the latest trials but also the rationale and proposed mechanisms of action of several novel agents. In 2010, sipuleucel-T became the first immunotherapy to earn FDA approval for the treatment of prostate cancer, based on a 4.1-month overall survival advantage. Since that time, a number of other immunotherapies have been studied in prostate cancer, with 2 of them in ongoing phase III trials: PROSTVAC, a therapeutic vaccine directed against PSA and enhanced by the addition of 3 co-stimulatory molecules, and ipilimumab, a monoclonal antibody targeting the T-cell inhibitory receptor CTLA-4. The PROSTVAC study is a 3-arm, placebo-controlled trial of PROSTVAC ± GM-CSF in patients with mCRPC. Ipilimumab is under investigation in 2 placebo-controlled phase III trials – one in patients with chemotherapy-naïve CRPC, and the other in patients who have already received docetaxel and will receive radiation therapy, which is believed to prime the immune system via release of radiation-induced dead cells. Results from these phase III immunotherapy trials are expected in the next 6 to 18 months.

    One of the notable characteristics about immunotherapies as a class is their unique response profile: immunotherapies may take longer to elicit a response compared with traditional chemotherapy regimens, and frequently elicit no objective responses at all. However, the lack of a measurable response does not impact the survival benefit. This can be illustrated by the IMPACT trial, in which sipuleucel-T demonstrated an impressive 4.1-month survival advantage despite inducing a partial objective response in only 1 patient.
Click here to download PDF version

Physicians’ Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
This activity is not approved for AMA PRA Category 1 Credit™.
Supported by educational grants from Astellas and Medivation, Bayer HealthCare Pharmaceuticals, Dendreon, Ferring Pharmaceuticals, Inc., and Millennium: The Takeda Oncology Company.

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