CHICAGO, IL USA (UroToday.com) - Presented by Charles J. Ryan, MD1 on behalf of Anil Londhe,2 Arturo Molina,3 Matthew R. Smith,4 Johann S. de Bono,5 Peter F.A. Mulders,6 Dana Rathkopf,7 Fred Saad,8 Christopher J. Logothetis,9 Karim Fizazi,10 Howard I. Scher,7 Eric J. Small,1 Shannon Matheny,3 Thian Kheoh,3 and Thomas W. Griffin3 at the American Society of Clinical Oncology (ASCO) Annual Meeting - May 31 - June 4, 2013 - McCormick Place - Chicago, IL USA
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1Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; 2Janssen Research & Development, Raritan, NJ; 3Janssen Research & Development, Los Angeles, CA; 4Massachusetts General Hospital Center, Boston, MA; 5Institute of Cancer Research and Royal Marsden Hospital, Sutton, UK; 6Radboud University Medical Centre, Nijmegen, The Netherlands; 7Memorial Sloan-Kettering Cancer Center, New York, NY; 89MD Anderson Cancer Center, Houston, TX; 10Institut Gustave Roussy, University of Paris Sud, Villejuif, France
ABSTRACT:
Relationship of baseline PSA and degree of PSA decline to radiographic progression free survival (rPFS) in patients with chemotherapy-naive metastatic castrationresistant prostate cancer (mCRPC): Results from COU-AA-302
Charles J. Ryan, Anil Londhe, Arturo Molina, Matthew R. Smith, Johann Sebastian De Bono, Peter Mulders, Dana E. Rathkopf, Fred Saad, Christopher Logothetis, Karim Fizazi, Howard I. Scher, Eric Jay Small, Shannon Matheny, Thian San Kheoh, Thomas W. Griffin
Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA; Janssen Research & Development, LLC, Raritan, NJ; Janssen Research & Development, LLC, Los Angeles, CA; Massachusetts General Hospital Cancer Center, Boston, MA; The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; Radboud University Medical Centre, Nijmegen, Netherlands; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Montreal, Montreal, QC, Canada; The University of Texas MD Anderson Cancer Center, Houston, TX; Institut Gustave Roussy, University of Paris Sud, Villejuif, France
Background: Abiraterone acetate (AA), an androgen biosynthesis inhibitor, prolongs overall survival (OS) in mCRPC patients and is approved for use in this population. The relationship of PSA kinetics to rPFS was evaluated in an exploratory analysis of patients from COU-AA-302, a randomized phase III study of AA in chemotherapy-naive mCRPC patients.
Methods: 1,088 patients were randomized 1:1 to AA (1 g) + prednisone (P) (5 mg BID) or P alone. rPFS and OS were co-primary endpoints. rPFS was defined as time to first occurrence of bone scan progression by PCWG2 criteria, progression by CT/MRI by modified RECIST 1.0 criteria, or death from any cause; PSA changes were not a factor in determining rPFS. Quartiles of baseline PSA and % PSA decrease from baseline to nadir were analyzed. Stratified Cox regression models were used with factors for treatment, PSA outcomes, and baseline covariates performed at 55% of OS events.
Results: 54/546 patients (10%) in AA + P arm achieved undetectable PSA vs 14/542 patients (3%) in the P arm; at median follow-up of 27.1 mos, radiographic progression was observed in 28% (AA + P) vs 50% of patients (P). There was a consistent trend of decreasing hazard of progression with decreasing baseline PSA and increasing % PSA decline. Treatment effect of AA + P vs P with decreasing baseline PSA or % PSA decline remained significant (p50.001) after adjusting for other factors (PSA, LDH, alk phos, hemoglobin, bone metastasis) in the model.
Conclusions: rPFS was positively associated with the magnitude of PSA decline and inversely associated with baseline PSA. These effects remained after correcting for covariates. In all analyses, treatment with AA led to rPFS outcomes superior to P. Clinical trial information: NCT00887198.
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Charles J. Ryan, MD 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 (UCSF) where he is the leader of the Genitourinary Medical Oncology Program. He received his MD from the University of Wisconsin in Madison and completed his residency in internal medicine at the University of Wisconsin Hospital and Clinics, where he also served as chief resident. He completed a fellowship in medical oncology in the Department of Medicine at Memorial Sloan-Kettering Cancer Center and the Joan and Sanford I. Weill Medical College of Cornell University in New York.
His clinical and research work centers on the design and conduct of clinical trials of novel therapies for advanced prostate cancer, specifically secondary hormonal therapies targeting adrenal androgen signaling, insulin growth factor inhibitors, androgen receptor targeted therapy and chemotherapy. In addition to clinical trials, Dr. Ryan collaborates with many laboratories researching the role of the androgen receptor and other signaling mechanisms in prostate cancer patients.
Dr. Ryan is a member of several honor societies and is the recipient of a Leadership and Service Award and the John Kimberly Curtis Award from the University of Wisconsin Medical School. He received the American College of Physicians/American Society of Internal Medicine Evergreen Award in 2000 and the American Society of Clinical Oncology Merit Award and Cancer and Leukemia Group B: Young Investigator Award, both in 2003. He was awarded the Donald Coffey Career Development Award from the Prostate Cancer Foundation in 2006 and a California Coalition to Cure Prostate Cancer Award in 2007.
