ASCO 2017: Liquid Biopsies: Current Utility and Future Directions
Recent major clinical trials support the usage of advanced medications (chemotherapy and Abiraterone) given as early as possible, even in hormone naïve patients(CHAARTED1, STAMPEDE2, and the most recent LATITUDE3).
There has been a recently published meta-analysis of 9 phase 3 clinical trials in mCRPC, analyzing the influence of various metastatic sites on disease survival.4 This meta-analysis demonstrated that lymph node metastasis had the best median overall survival (OS) with 31.6 months, while visceral metastasis, especially hepatic metastasis, had the worst overall median survival of 13.5 months. For visceral metastatic disease there are several treatment options, including Enzalutamide and Platinum chemotherapy.
Dr. Lang continued his discussion on molecular evaluation in mCRPC that has been shown to have frequent copy number gains of 8q, as well as copy number losses of 8p, 13q, 16q, and 18q. Furthermore, there are androgen receptor alterations in 63% of cases, PI3K alteration in 49%, and DNA repair pathway alterations in 19% of cases.
Lastly, Dr. Lang discussed circulating biomarkers. These include cell free DNA, circulating tumor cells, circulating exosomes and the possibility of additional circulating factors. It is important to know that there are different biomarker categories, including: diagnostic, prognostic, predictive, pharmacodynamic, discovery and surrogate. It is important to know that discrimination of signal from noise is the greatest challenge in any blood biomarker assay. It has already been shown that CTC enumeration (through Cellsearch) is predictive of OS in mCRPC patients. Additionally, gene expression analysis of androgen receptor variant 7 in CTCs correlates with clinical outcomes, including PSA progression free survival (PFS), radiographic PFS and OS.
Unanswered questions include when and what to analyze, whether it is CTCs or ctDNA. In summary, the genomic landscape is evolving from localized to mCRPC. Additionally, molecular interrogation of mCRPC is now becoming standard of care. In conclusion, serial molecular evaluation and counseling of our patients is needed to provide optimal medical care. CTCs and ctCDNA have distinct contexts of use.
Presented By: Joshua Michael Lang, MD, University of Wisconsin
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
Twitter: @GoldbergHanan
REFERENCES:
1.Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. The New England journal of medicine 2015; 373(8): 737-46.
2.James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet (London, England) 2016; 387(10024): 1163-77.
3.Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. New England Journal of Medicine; 0(0): null.
4.Halabi S, Kelly WK, Ma H, et al. Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2016; 34(14): 1652-9.
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA