@article{6b0d2b4274eb4743a00e3a3c9c0a846e,
title = "Genomics-driven precision medicine for advanced pancreatic cancer: Early results from the COMPASS trial",
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 ¼ 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.",
author = "Aung, {Kyaw L.} and Fischer, {Sandra E.} and Denroche, {Robert E.} and Jang, {Gun Ho} and Anna Dodd and Sean Creighton and Bernadette Southwood and Liang, {Sheng Ben} and Dianne Chadwick and Amy Zhang and O'Kane, {Grainne M.} and Hamzeh Albaba and Shari Moura and Grant, {Robert C.} and Miller, {Jessica K.} and Faridah Mbabaali and Danielle Pasternack and Lungu, {Ilinca M.} and Bartlett, {John M.S.} and Sangeet Ghai and Mathieu Lemire and Spring Holter and Connor, {Ashton A.} and Moffitt, {Richard A.} and Yeh, {Jen Jen} and Lee Timms and Krzyzanowski, {Paul M.} and Neesha Dhani and David Hedley and Faiyaz Notta and Wilson, {Julie M.} and Moore, {Malcolm J.} and Steven Gallinger and Knox, {Jennifer J.}",
note = "Funding Information: This study was conducted with the support of the Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario. S. Gallinger is supported by the Ontario Institute for Cancer Research, a Canadian Cancer Society Research Institute grant (702316), a charitable donation from the Canadian Friends of the Hebrew University (Alex U. Soyka), and the Lebovic Chair in Hepatobiliary/ Funding Information: This study was conducted with the support of the Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario. S. Gallinger is supported by the Ontario Institute for Cancer Research, a Canadian Cancer Society Research Institute grant (702316), a charitable donation from the Canadian Friends of the Hebrew University (Alex U. Soyka), and the Lebovic Chair in Hepatobiliary/ Pancreatic Surgical Oncology. J.J. Yeh is supported by research grants (CA193650 and CA199064) awarded by the National Cancer Institute. Publisher Copyright: {\textcopyright} 2017 American Association for Cancer Research.",
year = "2018",
month = mar,
day = "15",
doi = "10.1158/1078-0432.CCR-17-2994",
language = "English (US)",
volume = "24",
pages = "1344--1354",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "6",
}