CHICAGO, IL USA (UroToday.com) - Presented by Raya Leibowitz-Amit, MD, PhD at the American Society of Clinical Oncology (ASCO) Annual Meeting - May 31 - June 4, 2013 - McCormick Place - Chicago, IL USA
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Novel predictive markers of PSA response to abiraterone acetate in men with metastatic castration-resistant-prostate-cancer (mCRPC)
Raya Leibowitz-Amit, Arnoud J. Templeton, Eshetu G. Atenafu, Francisco Emilio Vera-Badillo, Muralidharan Chllamma, Henry L. Solow, Jennifer J. Knox, Ian Tannock, Srikala S. Sridhar, Anthony Michael Joshua
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada; Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada; Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada; Princess Margaret Hospital, Toronto, ON, Canada
Background: Abiraterone acetate (AA) prolongs survival in men with mCRPC pre- and post- chemotherapy. To date, clinical predictive biomarkers of response remain poorly characterized. The aim of this retrospective study was to identify and analyze predictors of response to AA in men with mCRPC.
Methods: All men receiving AA at the Princess Margaret Cancer Centre between November 2009 and December 2012 were reviewed. PSA response rate (RR) was defined according to PCWG2 criteria and assessed 12 weeks after AA start. Potential predictive factors were analyzed using uni- and multivariable logistic regression models.
Results: In total, 70 patients were evaluable for response: 34 men were chemotherapy naive and had a PSA RR of 44% (95% CI 27-62%); 36 men had prior chemotherapy and had a PSA RR of 33% (95% CI 17-50%). In univariable analysis, pre-treatment lactate dehydrogenase (LDH) level > 220 U/L (ULN) and a neutrophil-to-lymphocyte ratio (NLR) > 5 were both significantly associated with a lack of PSA response. On multivariable analysis, NLR > 5 remained significantly associated with lack of a PSA response. Men were then stratified into three groups according to these two variables. These groups were significantly associated with RRs. PSA RR was not found to be associated with the Gleason score, initial stage, time from initial diagnosis to mCRPC or to AA initiation, prior ketoconazole or docetaxel treatment, pre-treatment alkaline phosphate or PSA doubling time.
Conclusions: A pretreatment NLR > 5 and an LDH > ULN were both strongly associated with a lack of PSA response to AA. These factors may be key in stratifying men into different response groups to AA.
Raya Leibowitz-Amit, MD, PhD received her BSc in biology from the Tel-Aviv university and her MSc in neurobiology from the Weizmann Institute of Science cum laude in 1999. At that point, she decided to become a physician, engaging in both MD and PhD studies from the Tel-aviv University in Israel in 2006. She was accepted to the 'Talpiot medical leadership program' at the Sheba medical center in 2007, enabling her to engage in basic laboratory research throughout her residency, during which she also received the 'best resident award' on behalf of the Israeli Cancer Association.
After becoming a certified medical oncologist in Israel in 2012, she worked as a clinician-investigator at the Sheba Medical Center, being the principal investigator of a lab studying the role of micro-RNAs in melanoma. Her major scientific work until now (first and last authorship) has been published in Nature Medicine, Cancer Research and Molecular Cancer. She is a recipient of the 'melanoma research alliance young investigator award.'
Dr. Leibowitz-Amit has recently shifted her clinical and research interests to genitourinary cancers, mainly concentrating on prostate cancer, with a special interest in cancer in the elderly population (onco-geriatrics). She is currently a clinical research fellow in the genitourinary oncology clinic at the Princess Margaret Hospital under the mentorship of Dr. Anthony Joshua, performing clinical and translational research in prostate cancer.