Molecular profiling of advanced pancreatic cancer (PC) patients from a phase I/II study using circulating tumor DNA
| Autor: | Clive Morris, Hedy L. Kindler, Daniel V.T. Catenacci, Greg Jones, Theodore Karrison, Emma Green, Samantha Lomnicki, Emily O'Day, Melissa Maranto, Michael Epstein |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 35:4124-4124 |
| ISSN: | 1527-7755 0732-183X 0106-4622 |
| DOI: | 10.1200/jco.2017.35.15_suppl.4124 |
| Popis: | 4124 Background: PC has a poor prognosis with a 5-year survival of 9%. Targeted therapies have yet to demonstrate improved outcomes in this disease. Circulating tumour DNA (ctDNA) may be used as a non-invasive method for the detection and quantification of genomic abnormalities. We performed a retrospective-prospective study to assess molecular alterations in the ctDNA of advanced PC patients. Methods: Plasma samples were banked from patients enrolled in the previously reported Phase Ib/II trial of gemcitabine with placebo or vismodegib (NCT01064622; Catenacci et al JCO 2015). Eligible patients had unresectable PC and no prior therapy for metastatic disease. Patient samples ( < 3ml) collected pre-treatment and at regular intervals and stored for ~6-8 years were analyzed using InVision (enhanced tagged-amplicon sequencing) for “hotspot” regions of 34 genes, including KRAS (exons 2 and 3), and select full gene coverage. Results: Of 113 patients enrolled in the trial, a cohort of 72 patients were included in this study. Baseline plasma ctDNA profiling detected any genomic event in 88% of patients (SNV/indels found at range of 0.07%-23% allele fraction (AF) with 20% detected at < 0.5% AF). Patients had between 1-5 mutations (median, 2): KRAS mutations were detected in 80% of patients tested, of which 86% had concurrent KRAS/TP53 mutation(s) and 16% with concurrent KRAS/TP53/CDK2NA. Of note, 2 cases presented with IDH1 point mutations (R132C, R132H). An ERBB2 amplification and a FGFR2 amplification were detected in 2 individuals. An update on the analyses will include serial ctDNA testing during treatment and correlation with outcomes. Conclusions: ctDNA analysis of this cohort of banked PC plasma samples described the landscape of genomic aberrations at baseline and over time, including rare but potentially important actionable events including ERBB2 and FGFR2 amplifications and IDH1 mutation. We demonstrate a sensitive method for re-analysing trial outcomes, despite limiting plasma volume and time lapse since samples were collected. |
| Databáze: | OpenAIRE |
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