A SINGLE INSTITUTION EXPERIENCE WITH GUARDANT360 LIQUID BIOPSY (LB) FOR THERAPEUTIC DECISION IN ADVANCED SOLID TUMORS

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. GUARDANT360, a blood-based liquid biopsy approach that analyzes circulating tumor DNA (ctDNA), offers a simple and comprehensive tool for real-time tumor NGS (next generation sequencing) genetic profiling in advanced refractory cancer patients. Methods: We studied the performance of GUARDANT360 in several advanced solid cancers already refractory to conventional therapy. GUARDANT360 is a single-molecule next-generation digital sequencing assay with ability to detect somatic mutations, gene fusions and copy number variations across a total of 74 actionable genes covering approximately 80 kbps and it also detects MSI (microsatellite instability). A total of 90 plasma samples (2 for each patient) of 45 patients with advanced solid tumors and refractory to convencional therapy were studied. Results: The overall detection rate of somatic pathogenic variants potentially actionable (PVPA) in ctDNA was 64% (29 patients) for all indications (the range of detectable ctDNA mutations was 0.03%-57%). The total number of PVPA in all 29 patients was 50 as follows. CRC: 12 (27%) tested, 23 PVPA: KRAS – 4, MSI-H -1, ATM – 2, FGFR1(amp)- 1, PIK3CA – 3, BRCA1 – 1, BRCA2 – 2, APC – 4, PTEN – 1, MTOR – 1, NF1 – 1, BRAF – 1, MAP2K1 -1. Pancreatic cancer: 7 (16%) tested, 4 PVPA: STK11 – 1, AKT1 – 1, APC – 1, FGFR1 amp- 1. NSCLC: 6(14%) tested, 4 PVPA: ALK-EML4 fusion – 1, ERBB2 (G776 Delins VC) – 1, ATM -2. Ovarian cancer: 3(7%), 3 PVPA: BRCA1 – 1, PIK3CA – 2. Breast cancer: 4(9%) tested, 7 PVPA: ESR1 – 2, PIK3CA -1, FGFR1 amp -2, ERBB2 amp -1, CCND1 – 1. Head and Neck: 2(4.5%) tested, 3 PVPA: PTEN – 1, PIK3CA – 1, FGFR1 amp – 1. CUP (carcinoma of unknown primary): 2 (4.5%) tested, 2 PVPA: CDK6 -1, FGFR1 amp – 1. Renal cancer: 1 tested, 2 PVPA: NF1 – 1, JAK2 -1. Prostate cancer: 1 (2%) tested, 1 PVPA: AR. NET: 1 (2%) tested, 1 PVPA: ATM. Conclusion: Our results suggest that GUARDANT360 LB is a highly feasible, comprehensive and sensitive LB technology and should be used for a routine laboratory detection of the important genomic variations to determine the targeted therapy in patients with varied advanced solid tumors with with clear benefits compared to tissue diagnosis.