San Francisco, CA (UroToday.com) -- Foundation Medicine, Inc. and its collaborators announced results from a prostate cancer study evaluating the landscape of genomic alterations identified by liquid biopsy in over 3,000 patients, as well as assessing concordance of liquid and tissue biopsy in over 800 patients. The study demonstrated high concordance between targetable alterations identified using circulating tumor DNA (ctDNA) and tissue-based comprehensive genomic profiling (CGP) in patients with metastatic castration-resistant prostate cancer (mCRPC). It also found that, in many patients, liquid biopsy detects more acquired resistance mechanisms than tissue biopsy. The study, “Genomic analysis of circulating tumor DNA (ctDNA) in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms,” was published online in Clinical Cancer Research, a journal of the American Association for Cancer Research. These data will also be presented as a poster highlight on Feb. 11 at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).
Prostate cancer is the second most common cancer in men; 1 in 9 will be diagnosed during their lifetime.1 mCRPC occurs when prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.2 Because there have previously been limited treatment options for this specific disease area, there is generally a high mortality rate. In this study, genomic analysis of plasma collected from 3,334 patients with advanced prostate cancer (including 1,674 samples collected from Clovis Oncology’s TRITON2 and TRITON3 trials in which Foundation Medicine’s liquid biopsy test was utilized to screen patients for enrollment) demonstrated that nearly all (94%) of patients had detectable ctDNA.
“One of the most important findings in this study is that the majority of patients with advanced prostate cancer have abundant circulating tumor DNA that can be tested using comprehensive genomic profiling to support doctors as they consider targeted therapies for their patients,” said Geoff Oxnard, M.D., VP, Global Medical Lead, Liquid Franchise at Foundation Medicine. “When tumor tissue is difficult to obtain, as is often the case in patients in mCRPC, liquid biopsy is a proven, minimally-invasive method to secure genomic insights, with the option to reflex to a tissue biopsy if ctDNA turns out to be insufficient to analyze.”Using the collected samples, researchers profiled the landscape of genomic alterations detected in ctDNA and assessed concordance with tissue-based CGP. Using Foundation Medicine’s liquid biopsy test, study investigators detected 93% of the BRCA1/2 mutations that had also been detected using tissue CGP. Additionally, they found that ctDNA harbored some BRCA1/2 alterations not identified by tissue testing. They concluded that the large percentage of mCRPC patients in the study with rich genomic signal from ctDNA, and the sensitive, specific detection of BRCA1/2 alterations, positions liquid biopsy as a compelling clinical complement to tissue CGP for these patients.
Further, a diverse variety of potential androgen receptor resistance alterations were detected in 42% of patients, which is higher than the percentage detected in the same patients’ tissue biopsies. This points to ctDNA’s capacity to provide a more comprehensive picture of the development of acquired resistance anywhere in the body than the testing of one lesion.
The poster highlight presentation will be available to ASCO GU registrants on Feb. 11 at 8 am:
- Abstract 25 - Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer to identify targetable BRCA alterations and AR resistance mechanisms.
- American Cancer Society Key Statistics for Prostate Cancer: https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html
- Cancer.Net. (2019). Treatment of metastatic castration-resistant prostate cancer. www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer