Co-sponsors of the 2013 Genitourinary Cancers Symposium announced today important research to be presented at this year‘s meeting, taking place February 14-16 at the Rosen Shingle Creek in Orlando, Florida.
Three of the featured studies focus on the prevention, diagnosis and treatment of prostate cancers; another study looks at a new immunotherapy for metastatic kidney cancer.
Thursday, February 14 Presentations
Abstract #10
Long-term survival of subjects in the prostate cancer prevention trial.
General Poster Session A
Thursday, February 14, 2013, 11:45 AM – 01:15 PM EST
Thursday, February 14, 2013, 05:05 PM – 06:35 PM EST
Rosen, Gatlin Ballroom B
Phyllis J. Goodman, M.S.
SWOG Statistical Center
Seattle, WA
―A randomized trial designed to evaluate finasteride as a chemopreventative agent in prostate cancer has been previously reported (NEJM 349:213-222, 2003) and demonstrated an almost 25% reduction in the risk of being diagnosed with prostate cancer over a 7-year period for those receiving finasteride as opposed to placebo; and an increased risk of higher Gleason grade tumors in those receiving finasteride, although it was unclear whether this latter finding represented a true change in the biology of the tumors in response to finasteride, or an artificial by-product on the way the trial was conducted. If finasteride truly affected the natural history of the cancer, then this should be reflected as a long-term reduction of survival in this group. In this report, with follow-up to 18 years, 7-year administration of finasteride does not decrease overall mortality from prostate cancer despite the diagnosis of higher grade tumors, but significantly reduces the risk of a prostate cancer diagnosis.
– Bruce J. Roth, MD
Member, 2013 Genitourinary Cancers Symposium News Planning Team
American Society of Clinical Oncology (ASCO)
Abstract #32
Validation of the biopsy-based genomic prostate score (GPS) as a predictor of high-grade or extracapsular prostate cancer to improve patient selection for active surveillance (AS).
General Poster Session A
Thursday, February 14, 2013, 11:45 AM – 01:15 PM EST
Thursday, February 14, 2013, 05:05 PM – 06:35 PM EST
Rosen, Gatlin Ballroom B
Matthew R. Cooperberg, MD, MPH
University of California, San Francisco
San Francisco, CA
―PSA based screening for prostate cancer has resulted in the increased diagnosis of many cases of clinically insignificant prostate cancer that will never harm a man in his lifetime. This has popularized the concept of active surveillance where patients are monitored rather than definitively treated for their localized prostate cancer. The development of this genomic prostate score (GPS) provides a unique new tool with more information than is currently routinely available to allow physicians and their patients to choose the prostate cancer active surveillance approach with confidence.
– Leonard G. Gomella, MD, FACS Member, 2013 Genitourinary Cancers Symposium News Planning Team
Society of Urologic Oncology (SUO)
Abstract #28
The effect of therapeutic anticoagulation on overall survival (OS) in men receiving docetaxel chemotherapy for metastatic castration-resistant prostate cancer (mCRPC).
General Poster Session A
Thursday, February 14, 2013, 11:45 AM – 01:15 PM EST
Thursday, February 14, 2013, 05:05 PM – 06:35 PM EST
Rosen, Gatlin Ballroom B
Caroline F. Pratz, CRNP
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, MD
―This study adds to the growing body of evidence that anticoagulants, including aspirin although not studied here, improve outcome following treatment for prostate cancer. These results are particularly compelling given the advanced nature of the disease in the study population. The ideal method of anticoagulation, dose, timing, and associated risks all need to be better defined and require further study. It is too early for men to begin taking anti-coagulants with the hope of improving the treatment for prostate cancer. Validation of these results are needed. However, men requiring anti-coagulation for other causes may also benefit in terms of controlling their prostate cancer.
– Mark K. Buyyounouski, MD
Member, 2013 Genitourinary Cancers Symposium News Planning Team
American Society for Radiation Oncology (ASTRO)
Saturday, February 16 Presentations
Abstract #357
Prolonged survival with personalized immunotherapy (AGS-003) in combination with sunitinib in unfavorable risk metastatic RCC (mRCC).
General Poster Session C
Saturday, February 16, 2013, 06:45 AM – 07:55 AM EST
Saturday, February 16, 2013, 11:50 AM – 01:05 PM EST
Rosen, Gatlin Ballroom B
Asim Amin, MD, PhD
Carolinas Medical Center
Blumental Cancer Center
Charlotte, NC
―Advanced metastatic kidney cancer carries a poor prognosis with newer oral medications and immunotherapy each showing some modest improvements in survival. This study uses a patient‘s own specific cancer fighting immune cells (AGS-003) in combination with a standard oral medication, sunitinib, known as a targeted therapy that blocks kidney cancer's specific pathways that contribute to cancer growth and survival. This novel combination therapy using patient specific immunotherapy combined with an oral agent showed significant benefits with a doubling of survival in patients with aggressive metastatic kidney cancer. This is very encouraging and will need to be confirmed in a larger number of patients.
– Leonard G. Gomella, MD, FACS Member, 2013 Genitourinary Cancers Symposium News Planning Team
Society of Urologic Oncology (SUO)
2013 Genitourinary Cancers Symposium News Planning Team
Bruce J. Roth, MD, American Society of Clinical Oncology (ASCO); Mark K. Buyyounouski, MD, American Society for Radiation Oncology (ASTRO); Leonard G. Gomella, MD, FACS, Society of Urologic Oncology (SUO).
Click here to view the disclosures for the News Planning Team. Relevant Information from Cancer.Net, ASCO’s cancer information website:
• - Cancer.Net Guide to Prostate Cancer
• - Cancer.Net Guide to Kidney Cancer
For information on progress against cancer, visit www.CancerProgress.Net.
Contact: Kelly Baldwin
February 12, 2013 571-483-1365
Onsite Phone: 407-996-7655
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Long-term survival of subjects in the prostate cancer prevention trial
Background: As finasteride could reduce by 25% the number of prostate cancers (PCa) diagnosed in the U.S. annually, the public health benefit of prostate cancer prevention could be enormous. We performed a survival analysis to assess for any evidence of increased risk of death in men randomized to finasteride, a potential indicator of a ‗true‘ increased risk of high grade (HG) disease in the PCPT.
Methods: A Social Security Death Index search was conducted on all randomized men to ascertain date of death. Cox proportional hazards models adjusting for known risk factors for overall survival and survival from time of diagnosis of PCa overall, low grade (LG) and HG were used to estimate hazard ratios (HR) and construct 95% confidence intervals to determine if survival on finasteride and placebo were equivalent.
Results: A total of 5,128 deaths have been reported; 2,584 men on finasteride and 2544 on placebo. 15-year survival rates for all randomized men in each arm is 78%. The HR for overall survival on finasteride compared to placebo is 1.04 (95% CI 0.96, 1.10, p=.19). 10-year survival from diagnosis for men with PCa was slightly higher for men randomized to finasteride (10-year survival 83% vs. 81%) but not statistically significant (HR= 0.87, 95% CI 0.73 - 1.04, p=.14). For the men with HG PCa, there was no evidence of worse survival on finasteride (HR= 1.01; 95% CI 0.73, 1.14, p=.97) while those diagnosed with LG disease finasteride had superior survival (HR= 0.73; 95% CI 0.57, 0.94, p=.01).
Conclusions: For men in PCPT with PCa there was no difference in survival from diagnosis date, a slightly-superior 10-year survival with finasteride and a statistically-superior survival among men with LG tumors in the finasteride group. A potential explanation for this phenomenon could be a lead-time bias. Arguing against this bias is the identical survival of HG PCa in both groups. Another potential explanation is that the men with LG PCa on placebo include a greater number with undetected HG disease; HG tumors in men on finasteride were more likely detected due to the improved performance of prostate biopsy. With follow-up of 18 years, finasteride administration for 7-years does not appear to affect mortality but significantly reduces the risk of a PCa diagnosis.
Disclosures: Nothing to disclose
Authors: Phyllis J. Goodman, Ian Murchie Thompson Jr., Catherine M. Tangen, Howard L. Parnes, Paul Alphonso Godley, Leslie G. Ford
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Background: Multiple guidelines endorse AS for low-risk prostate cancer; however, concerns regarding biopsy undersampling for grade and/or stage have limited its acceptance in practice. The 17-gene GPS was previously developed in 2 large studies to be a biopsy-based predictor of adverse pathology and clinical recurrence. We conducted a validation study to determine whether GPS improves prediction—from paraffin-embedded biopsy tissue—of true grade and stage over clinical criteria alone.
Methods: Radical prostatectomy (RP) patients at UCSF with clinical low or low-intermediate risk prostate cancer (biopsy Gleason score (bGS) 3+3, or 3+4 in ≤3 cores; PSA ≤20; clinical stage ≤T2) with ≥1mm biopsy tumor length were eligible. Central review of both biopsy and RP pathology was required. GPS, on a 0-100 scale, was assessed by quantitative RT-PCR in manually microdissected biopsy tumor tissue. Univariate and multivariable multinomial logistic regression was used to test association with adverse pathology (primary Gleason 4, minor Gleason 5, and/or stage pT3 at RP).
Results: Of 412 eligible men, RT-PCR was successful in 395 (96%), including 99.5% of those with ≥10ng RNA yield and 88% of those with < 2mm tumor length. 123 (31%) had adverse pathology. In the primary analysis, GPS predicted adverse pathology (p=0.002) controlling for bGS. GPS predicted both high grade (OR 2.3 per 20 GPS units, 95%CI 1.5-3.7, p < 0.001) and pT3 (OR 1.9 per 20 GPS units, 95%CI 1.3-3.0, p=0.003). In multivariable analysis, GPS strongly predicted adverse pathology (p < 0.005) after controlling for the well-validated CAPRA score or other standard pretreatment factors (alone or in combination). For example, the proportion of men with >85% probability of freedom from adverse pathology increased from 5% with CAPRA alone to 22% with CAPRA+GPS.
Conclusions: GPS is a validated, biopsy-based predictor of adverse prostate cancer pathology. Incorporating GPS with clinical data provides substantially improved risk discrimination, and enables more accurate identification of a larger population of patients who can choose AS more confidently as an initial management strategy.
Authors: Matthew R. Cooperberg, MD, MPH, Janet E. Cowan, MA, Jeffry P. Simko, MD, PhD, Tara Maddala, PhD, June M. Chan, ScD, Athanasios C. Tsiatis, MD, FCAP, Imelda Tenggara-Hunter, Dejan Knezevic, PhD, Frederick L. Baehner, MD, Steven Shak, MD, Mark Lee, MD, PhD, Peter Carroll, MD, MPH
Disclosures: Matthew R. Cooperberg, MD, MPH Consultant or Advisory Role GenomeDx Biosciences, Genomic Health, Jeffry P Simko, MD, PhD, stock ownership in Genomic Health and research funding Genomic Health and GenomeDx Biosciences, Tara Maddala, PhD Director, Biostatistics, Genomic Health, stock ownership in Genomic Health, June M. Chan, ScD Senior Manager, Clinical Liason, Myriad Genetics, stock ownership in Genomic Health and Myriad Genetics, research funding from Genomic Health, GenomeDx Biosciences, Myriad Genetics, Athanasios C. Tsiatis, MD, FCAP Pathologist, Genomic Health, stock ownership in Genomic Health, Frederick L. Baehner, MD Senior Director, Pathology, Genomic Health, stock ownership in Genomic Health, Steven Shak, MD Chief Medical Officer, Genomic Health, stock ownership in Genomic Health, Mark Lee, MD, PhD Vice President, Oncology Development, Genomic Health, stock ownership in Genomic Health, Peter Carroll, MD, MPH Consultant or Advisory Role with GenomeDx Biosciences, research funding from Myriad Genetics.
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Background: Anticoagulants have been postulated to possess antitumor activity, although clinical data supporting this claim are conflicting. We sought to examine the effect of therapeutic anticoagulation on OS in men with mCRPC receiving first-line docetaxel chemotherapy.
Methods: We retrospectively reviewed the records of 247 consecutive mCRPC patients who received first-line docetaxel chemotherapy between 1/1/1998 and 1/1/2010. Information on anticoagulant use, type of anticoagulant administered, indication for anticoagulation, and duration of anticoagulation were captured. Univariate and multivariable Cox proportional hazards regression models were developed to investigate the effect of anticoagulant use on OS.
Results: In all, 29/247 men (11.7%) received anticoagulation (LMW heparin: 17/247; warfarin: 12/247). The indication was DVT in 15/247, PE in 9/247, and both DVT and PE in 5/247 men. In univariate analysis, anticoagulant use was associated with improved OS (any anticoagulant, HR 0.61 [95%CI 0.40–0.94] P=0.024; LMW heparin, HR 0.58 [95%CI 0.34–0.99] P=0.048; warfarin, HR 0.82 [95%CI 0.55–1.28] P=0.23). Median OS was 20.9 mo (with any anticoagulant) versus 17.1 mo (with no anticoagulant). In multivariable analysis, anticoagulant use remained a significant predictor of OS after adjusting for other prognostic factors.
Conclusions: Anticoagulant use is an independent predictor of OS in men with mCRPC receiving docetaxel. This finding is surprising given that the occurrence of venous thrombosis might be expected to negatively influence OS. If validated, these data may provide the impetus to explore the antitumor potential of anticoagulants in prospective clinical trials.
Authors: Caroline F. Pratz, Robert A. Brodsky, Emmanuel S. Antonarakis
Disclosures: Nothing to disclose.
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Background: During the past decade, VEGF targeted therapies have become standard treatment for advanced RCC. While targeted therapies have yielded improved efficacy, durable remissions are rare, particularly in unfavorable risk subjects.In a pivotal trial, treatment with sunitinib yielded a median OS of 5.3 months for poor risk and 20.7 months for intermediate risk subjects. Similarly, the validation dataset for the Heng risk model (ASCO 2011) revealed a median OS of 8 months for poor risk and 21 months for intermediate risk patients treated with VEGF targeted therapies. Durable responses have been elicited by immunotherapy in RCC. We report an update on patients with mRCC treated with combined VEGF TKI (sunitinib) plus autologous immunotherapy (AGS-003). Methods: In this phase II study, subjects with unfavorable prognosis mRCC (poor and intermediate risk) were treated with sunitinib plus autologous dendritic cell immunotherapy (AGS-003). Treatment consisted of standard 6-week cycles of sunitinib plus AGS-003 (once every 3 weeks x5 doses, then every 12 weeks until PD). Tumor response was assessed per RECIST and subjects were followed for PFS and OS. Immune monitoring samples were taken at screening, baseline and after the third and fifth doses of AGS-003 and analyzed by multiparametric flow cytometry.
Results: 21 subjects were treated. As previously reported, the median overall PFS was 11.2 months and the final median OS was 30.2 months. When analyzed by baseline Heng risk status, the median PFS was 19.4 months for intermediate (n=11) and 5.8 months for subjects with poor risk features (n=10) at baseline. The median OS is 39.5+ months for intermediate and 9.1 months for subjects with poor risk.
Conclusions: The results from this single-arm phase II study represents a near doubling of expected PFS and OS for unfavorable risk subjects treated with AGS-003 plus sunitinib.Updated survival and immunologicfindings will be presented, as 8 of 21 subjects are still alive and continue to be followed. These results support the ongoing phase 3 ADAPT study, which is designed to validate these encouraging clinical and immunologic findings.
Authors: Asim Amin, Arkadiusz Dudek, Theodore Logan, Raymond S. Lance, Jeffrey M. Holzbeierlein, Viraj A. Master, Sumanta Kumar Pal, Jennifer J. Knox, Lawrence Ivan Karsh, Doug Plessinger, Charles A. Nicolette, Robert A. Figlin
Disclosures: Asim Amin, MD, PhD, Arkadiusz Dudek, MD, PhD, and Theodore Logan, MD Consultant or Advisory Role with Argos Therapeutics, Doug Plessinger, RPh, VP, Clinical and Medical Affairs, Argos Therapeutics, Consultant or Advisory Role with Axcelo MSL Solutions, stock ownership in Argos Therpeutics, Charles A. Nicolette, PhD, VP, Research and Development, Argos Therapeutics, stock ownership in Argos Therapeutics.