Abstract IA15: Liquid biopsies: Implications for therapeutic response/resistance and prognosis

Liquid biopsies generally consist of genomic tests performed on tumor-derived circulating cell-free DNA (cfDNA) or circulating tumor cells (CTCs). Our experience pertains mostly to cfDNA, as we have performed almost 6,000 clinical-grade cfDNA analyses on our patients with cancer as part of our precision medicine efforts. We have found that cfDNA can be useful for the following: Matching patients with targeted drugs based on genomic markers. Detecting emerging resistance genomic alterations (often months before imaging findings indicate progression). Early detection of response after targeted agents—sometimes within the first week of therapy. Differentiating pseudoprogression from progression or hyperprogression after immunotherapy. Determining predictive markers for immunotherapy such as mutational burden and microsatellite instability status. Determining prognosis (including after surgery) based on number of cfDNA alterations and/or mutant allele frequency (%cfDNA). Advantages of blood-derived cfDNA (as compared to tissue DNA) testing include the following: No invasive tissue biopsy is necessary. cfDNA reflects shed DNA from multiple tumor sites (whereas tissue DNA reflects only the small piece of tissue biopsied). Serial blood samples for monitoring are feasible (as compared to serial tissue biopsies). Taking a blood sample is less expensive than acquiring a tissue biopsy. Quicker turnaround time for blood sample versus tissue because there is no need to do biopsy or to locate and obtain tissue sample from pathology. Disadvantages of cfDNA (compared to tissue DNA) testing include: Only small amounts of cfDNA are shed into the blood, necessitating very sensitive techniques to detect alterations. cfDNA levels can be suppressed by therapy. Most clinical-grade cfDNA panels are considerably smaller than current tissue DNA panels assessed by next-generation sequencing. cfDNA results (as compared to tissue DNA) may be more prone to being confounded by genomic alterations derived from clonal hematopoiesis of indeterminate potential. cfDNA analysis does not provide results of potential functional impact of therapeutic interventions; other liquid biopsies such as those utilizing CTCs may be useful in this way. Overall, our experience indicates that liquid biopsies are transformative tests that can be interrogated in myriad ways that help predict prognosis and impact treatment of patients with cancer. Disclosures: Dr. Kurzrock has the following disclosure information: Stock and Other Equity Interests (IDbyDNA, CureMatch, Inc., and Soluventis); Consulting or Advisory Role (Gaido, LOXO, X-Biotech, Actuate Therapeutics, Roche, NeoMed, Soluventis, and Pfizer); Speaker’s fee (Roche); Research Funding (Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Guardant Health, Grifols, Konica Minolta, DeBiopharm, Boerhringer Ingelheim, and OmniSeq [All institutional]); Board Member (CureMatch, Inc). Dr. Kato has no disclosures. Citation Format: Razelle Kurzrock, Shumei Kato. Liquid biopsies: Implications for therapeutic response/resistance and prognosis [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA15.