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Clin Cancer Res. 2018 Mar 15;24(6):1344-1354. doi: 10.1158/1078-0432.CCR-17-2994. Epub 2017 Dec 29.

Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer: Early Results from the COMPASS Trial.

Author information

1
Wallace McCain Centre for Pancreatic Cancer, Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
2
Department of Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
3
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
4
PanCuRx Translational Research Initiative, Ontario, Institute for Cancer Research, Toronto, Ontario, Canada.
5
UHN Biobank, University Health Network, Toronto, Ontario, Canada.
6
Genomics, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
7
Diagnostic Development, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
8
Joint Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Ontario, Canada.
9
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
10
Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
11
Department of Biomedical Informatics, Stony Brook University, Stony Brook, New York.
12
Department of Surgery, University of North Carolina, Chapel Hill, North Carolina.
13
British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
14
Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada.
15
Wallace McCain Centre for Pancreatic Cancer, Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. Jennifer.Knox@uhn.ca.

Abstract

Purpose: To perform real-time whole genome sequencing (WGS) and RNA sequencing (RNASeq) of advanced pancreatic ductal adenocarcinoma (PDAC) to identify predictive mutational and transcriptional features for better treatment selection.Experimental Design: Patients with advanced PDAC were prospectively recruited prior to first-line combination chemotherapy. Fresh tumor tissue was acquired by image-guided percutaneous core biopsy for WGS and RNASeq. Laser capture microdissection was performed for all cases. Primary endpoint was feasibility to report WGS results prior to first disease assessment CT scan at 8 weeks. The main secondary endpoint was discovery of patient subsets with predictive mutational and transcriptional signatures.Results: Sixty-three patients underwent a tumor biopsy between December 2015 and June 2017. WGS and RNASeq were successful in 62 (98%) and 60 (95%), respectively. Genomic results were reported at a median of 35 days (range, 19-52 days) from biopsy, meeting the primary feasibility endpoint. Objective responses to first-line chemotherapy were significantly better in patients with the classical PDAC RNA subtype compared with those with the basal-like subtype (P = 0.004). The best progression-free survival was observed in those with classical subtype treated with m-FOLFIRINOX. GATA6 expression in tumor measured by RNA in situ hybridization was found to be a robust surrogate biomarker for differentiating classical and basal-like PDAC subtypes. Potentially actionable genetic alterations were found in 30% of patients.Conclusions: Prospective genomic profiling of advanced PDAC is feasible, and our early data indicate that chemotherapy response differs among patients with different genomic/transcriptomic subtypes. Clin Cancer Res; 24(6); 1344-54. ©2017 AACR.

PMID:
29288237
PMCID:
PMC5968824
[Available on 2019-03-15]
DOI:
10.1158/1078-0432.CCR-17-2994

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