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Use of the GUARDANT360 noninvasive tumor sequencing assay on 300 patients across colorectal, melanoma, lung, breast, and prostate cancers and its clinical utility.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Analysis of genomic alterations in advanced malignant disease is quickly becoming the standard of care in oncology. Biopsies are risky, often costly and may not capture genetic changes that can emerge over time or in response to therapy. In contrast, GUARDANT360, a blood-based liquid biopsy approach that analyzes circulating tumor DNA (ctDNA), offers a simple and comprehensive tool for real-time tumor genetic profiling in advanced refractory cancer patients. Methods: We studied the performance of GUARDANT360 in five prevalent cancers: colorectal, melanoma, lung, breast, and prostate. Over 500 plasma samples and 100 matched tumors from a total of 300 unique patients were analyzed using GUARDANT360, a single-molecule next-generation digital sequencing assay with ability to detect somatic mutations and copy number variations with exquisite sensitivity. The assay covers sequences across a total of 54 actionable genes covering approximately 80 kbps. Select patients were treated on the basis of ctDNA alterations detected by GUARDANT360. Results: The overall detection rate of somatic alterations in ctDNA approached 85% for all indications (the range of detectable ctDNA mutations was 0.03%-87%). The concordance of tumor mutations to GUARDANT360 ranged from 67% (blood draw > 6 months post biopsy) to 93% (concurrent blood draw at time of biopsy). The dominant genetic mutations observed were similar to those previously reported for solid tumors. About 60% of cases with colorectal, breast and lung cancers had actionable mutations. The select patients treated on the basis of observed ctDNA alterations exhibited significant positive clinical outcomes (PR) suggesting strong potential for clinical utility of ctDNA sequencing. Conclusions: Advances in single-molecule sequencing and bioinformatics make possible the ultra-sensitive detection of somatic mutation and amplifications. Comprehensive profiling of ctDNA shows reasonable concordance to tumor profiles and illustrates the potential to improve the care of advanced refractory cancer patients.
Abstracts by AmirAli Talasaz:
Blood-based genomic profiling of circulating cell-free tumor DNA (ctDNA) in 1397 patients (pts) with colorectal cancer (CRC).Meeting: 2017 Gastrointestinal Cancers Symposium | Abstract No: 584
Cell free circulating tumor DNA (ctDNA) landscape in patients with advanced gastroesophageal adenocarcinoma (GEC).Meeting: 2017 Gastrointestinal Cancers Symposium | Abstract No: 47
Circulating tumor (ct)-DNA alterations in advanced urothelial carcinoma: Association with outcomes and evolution with therapy.Meeting: 2017 Genitourinary Cancers Symposium | Abstract No: 334