In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e15794-e15794
Abstract:
e15794 Background: Current treatment of pancreatic ductal adenocarcinoma (PDAC) is FOLFIRINOX or gemcitabine + nab-paclitaxel, and CA19-9 is the only approved biomarker to monitor tumor response. However, CA19-9 has several limitations (i.e. sensitivity and specificity), highlighting the need for new biomarkers. Being the majority of PDAC (75-95%) KRAS mutated (mutKRAS), the present study developed an analysis tool based on circulating tumor DNA (ctDNA) to monitor the variation of mutKRAS in PDAC undergoing first-line chemotherapy. Early variation of ctDNA mutKRAS after 15 days of treatment was correlated with response to therapy. Methods: Three ml of plasma were collected from patients with PDAC undergoing first-line FOLFIRINOX or gemcitabine + nab-paclitaxel. Patients underwent standard disease evaluation by imaging according to RECIST 1.1 criteria. Blood samples were drawn prior to cycle 1, after 14 days and at each radiological evaluation. ctDNA was extracted using a QIAmp Circulating nucleic acid Kit (Qiagen, Valencia, CA) and the KRAS codon 12 and p.G13D analysis was performed by digital droplet PCR (ddPCR, BioRad, Hercules, CA). Results: A total of 27 patients with locally advanced (15%) and metastatic (85%) PDAC were included in this study. mutKRAS in ctDNA was detected in 19 patients (70.3%) at baseline. There were no statistically significant differences in median PFS and OS in patients with baseline positive or negative ctDNA mutKRAS (p = 0.15). However, there was a statistically significant difference in PFS and OS between patients with increase vs. stability/reduction of ctDNA at the 14 day-evaluation (median PFS: 2.5 vs 7.5 months, p = 0.03; median OS: 9 vs 11.5 months p = 0.009). The imaging evaluation performed at 2 months after initiation of therapy demonstrated that all patients with an increase in ctDNA at 14 days had radiological progression of disease. Conclusions: The results of this pilot study support the use of ctDNA as a new marker for monitoring treatment outcome and disease progression in PDAC, suggesting that ctDNA mutKRAS is a non-invasive predictive factor of response in PDAC.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.e15794
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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