ASCO 2017: Emerging Biomarkers of Chemotherapy Resistance

Chicago, IL ( Dr. Karen Knudsen gave a summary of abstracts 5012, 5013, and 5014. She began with a short introduction on metastatic castrate resistant prostate cancer (mCRPC), emphasizing that strategies are needed to personalize medicine in this entity. At this point in time all mCRPC patients are treated similarly. Importantly, one should know that mCRPC is incurable and that resistance to first line hormonal therapy ultimately develops. The key questions are: Who is the right patients to receive novel therapy? What is the optimal sequencing of these agents and does it matter? For how long are these agents to be given and if they are beneficial? Why is there still relapse?

Dr. Knudsen then began with Abstract 5012 – Benefit of combining Docetaxel to androgen deprivation therapy in localized and metastatic in castrate sensitive prostate cancer is predicted by ERG status: an analysis of two GETUG 3 trials. The goal was to use pre-treatment core biopsies and explore predictive values of 3 candidate biomarkers (ERG, KI67 and PTEN). Key findings include that PTEN fails to predict for chemotherapy associated recurrence free survival (RFS), KI67 has limited predictive value, and ERG+ is associated with improved RFS and progression free survival (PFS).

Dr. Knudsen moved on to abstract 5013 – The aggressive variant prostate cancer (AVPC) molecular signature (MS) and platinum sensitivity in CRPC. This study focuses on the variant aggressive histology of prostate cancer. The AVPC can be diagnosed clinically by having 1/7 known distinct clinical features. AVPC can also be diagnosed with a distinct molecular signature, defined as combined tumor suppression defects of 2 or more alterations of tp53, RB1 and or PTEN by genomic analysis or immunohistochemistry. The basis for this investigation was a phase 2 randomized clinical trial comparing Cabazitaxel (CABAZ) to CABAZ + carboplatin in mCRPC. The authors tried to analyze whether AVPC-MS predict for platinum benefit. Key findings include the fact that adding Carboplatin to CABAZ is safe and improves progression free survival and response rates in mCRPC men. Lastly, AVPC-MS is a better predictor for platinum benefit than AVPC-C. These findings need to be validated in order to move forwards.

The final abstract 5014 – post hoc analysis of a phase 3 study to test the association between circulating methylated Glutathione S transferase (Mgstp1) DNA levels and response to docetaxel in mCRPC. Mgstp1 is inactivated in prostate cancer in over 90% of cases, it is detected twice as much in plasma free DNA than in DNA from CTCs. It has been shown in the past that Mgstp1 after 1 cycle of docetaxel was associated with overall survival (OS). In the current study, authors showed that early changes in Mgstp1 predict OS more accurately than PSA, suggesting its possible role as an early surrogate marker.

Dr. Knudsen concluded her presentation by stating what’s on the agenda for biomarkers in the future. Firstly, biomarker prioritizing must be done, testing of prostate cancer approved biomarkers should be performed as well, development of clinically applicable tests with appropriate standards, understanding the role of stroma/tumor microenvironment biomarkers. Finally, there is a need to consider limitations and advantages of variant tissue collection sources.

Presented By: Karen E. Knudsen, PhD, The Sidney Kimmel Cancer Center at Thomas Jefferson University

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @GoldbergHanan

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA


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