ASCO GU 2018: Incorporating Genomics Into the Management of Systemic Therapy: Advances and Practicality

San Francisco, CA (UroToday.com) Dr. Kim Chi gave an excellent talk on the incorporation of genomics into the management of systemic therapy. Dr. Chi began his presentation with stating some key points. Genomic profiling of castrate resistant prostate cancer (CRPC) tissues reveals driver aberrations that are clinically relevant. Circulating tumor DNA (ct DNA) is an effective tool to identify mutations and copy number changes in men with CRPC. Deleterious genomic alterations have been associated with treatment outcomes and have the potential to inform patient management. The challenge is to find the next best treatment for patients entering the CRPC state.

Liquid biopsies is an invaluable tool for the diagnosis of relevant genomic alterations. They are minimally invasive, enable serial sampling in large populations and in non-specialized centers. DNA is released into the blood by all cells = cell free DNA. In cancer patients, a proportion of cfDNA is tumor derived = circulating tumor DNA (ctDNA). The fraction of ctDNA/cfDNA is associated with disease burden and proliferation (Figure 1). Higher levels of ctDNA have been associated with higher tumor burden and worse treatment outcome. There is also a high concordance between matched ctDNA and biopsies, with 94% of mutations detected in metastatic tissue biopsy also detected in ctDNA. Furthermore, baseline ctDNA genomic alterations are associated with Abiraterone/Enzalutamie treatment outcomes.

There are currently several ongoing PARP inhibitor trials for CRPC (Figure 2). Dr. Chi also talked about the IRONMAN initiative – the international registry for men with advanced prostate cancer, involving researchers from the US, Canada, Brazil, Ireland, Sweden, Switzerland, and United Kingdom researching this genomics field. Dr. Chi also mentioned the Canadian Cancer Trials Group (CCTG) Umbrella trial for metastatic CRPC patients, attempting to ascertain the effect of different treatment options for these patients (Figure 3).

In summary, genomic profiling of CRPC tissues reveals driver aberrations that are informative and actionable. CtDNA can be used to identify genomic alterations in the majority of men with metastatic CRPC, and are representative of metastatic tissue biopsies. Lastly, deleterious genomic alterations, such as DNA repair genes, PI3K pathway, and androgen receptor, have been associated with outcomes and have the potential to inform patient management.

Figure 1 - The fraction of ctDNA/cfDNA is associated with disease burden and proliferation:

Figure 1

Figure 2 – Ongoing PARP inhibitor trials for CRPC

Figure 2

Figure 3 – The Canadian Cancer Trials Group (CCTG) Umbrella trial for metastatic CRPC patients

Figure 3



Presented by: Kim Chi, Univesity of British Columbia, Vancouver, Canada

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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