Abstract 5358
Background
Predictive mutational and transcriptional features in advanced PDAC are urgently needed for improved patient stratification and treatment selection.
Methods
As part of the COMPASS trial patients (pts) with advanced PDAC are prospectively recruited prior to first-line combination chemotherapy for whole genome sequencing (WGS) and RNA sequencing (RNASeq). Fresh tumor tissue is acquired by percutaneous core needle biopsy. Laser capture microdissection ensures high-resolution genomic analyses with results available within 8 wks. Tumor responses and clinical outcomes in this update were correlated with molecular characteristics.
Results
121 pts underwent a biopsy between December 2015 and April 2018; WGS and RNASeq were successful in 120 (99%) and 119 (98%) respectively, meeting all QC endpoints. 113 genomes have been reported in pts planned to receive chemotherapy; the median time from biopsy to report was 35.5 days. The median age was 63 years (29-81), 53% were male, and 17 (15%) had locally advanced disease. 20 pts (18%) were non evaluable for response. 64 (57%) received modified FFX as first line treatment. 24 (21%) tumors displayed the Moffitt basal-like RNA expression signature which associated with chemotherapy resistance, with tumor shrinkage mainly observed in the classical RNA subtype (p = 0.002). GATA6 expression (log10 scale) clearly separated Moffitt subgroups with classical tumors exhibiting high expression (p < 0.0001). EGFR overexpression was associated with the basal subtype (p = 0.002). The tumor of 1 pt at progression, switched from a basal to a classical phenotype. Of 89 pts with ≥ 6 months follow-up, median overall survival in the classical group was 10 mths vs. 5.1 months in the basal group (HR 0.32 95% CI 0.16–0.68, p = 0.0025). Signatures of homologous recombination deficiency were found in 4 pts (4%) including 2 with germline BRCA2 mutations, 1 of which was newly detected. 2 of 3 pts with a novel duplicator phenotype responded to folfirinox. 30% of pts had potentially actionable genetic alterations.
Conclusions
Prospective comprehensive profiling of advanced PDAC indicates that chemotherapy response differs according to genomic/transcriptomic subtypes, providing strong rationale for improved first line trial design.
Clinical trial identification
NCT02750657.
Legal entity responsible for the study
University Health Network.
Funding
Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario. Wallace McCain Centre for Pancreatic Cancer Pancreatic Cancer Canada Foundation Princess Margaret Cancer Foundation Wallace McCain Centre for Pancreatic Cancer Pancreatic Cancer Canada Foundation Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario Princess Margaret Cancer Foundation.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5720 - Evaluation of stemness and proliferation of human breast cancer stem cells (ALDH+) supplemented with heat-activated TGF-beta1 in the secretomes of stem cells from human exfoliated deciduous teeth (SHED)
Presenter: Septelia Wanandi
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4844 - Estrogen-related receptor _ as a potential molecular target for endometrial cancer therapy
Presenter: TETSUYA KOKABU
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1200 - Good tolerability and limited target-specific tissue distribution of an anti-L1CAM antibody administered to cynomolgus monkey indicates favorable safety profile of L1CAM-targeting therapies
Presenter: Jacques Gaudreault
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2905 - Pharmacokinetic drug-drug interaction between mitotane and etoposide in the treatment of adrenocortical carcinoma
Presenter: Anne Jouinot
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2597 - Real-world dosing of regorafenib (REG) in metastatic colorectal cancer (mCRC): final results from the prospective, observational CORRELATE study
Presenter: Juan Manuel O'Connor
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2663 - Safety and efficacy of trifluridine/tipiracil (FTD/TPI) in metastatic colorectal cancer (mCRC) patients according to previous treatment with regorafenib in the international phase 3b PRECONNECT study
Presenter: Julien Taieb
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1670 - Treatment pattern and outcomes of trifluridine/tipiracil therapy for metastatic colorectal cancer in the real-world data from the JFMC50 study
Presenter: Takeshi Kawakami
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1088 - Phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients (pts) over 70 with previously treated metastatic colorectal adenocarcinoma (mCRC) FFCD 1404 - REGOLD
Presenter: thomas Aparicio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2548 - Prospective Evaluation of Regorafenib Dose Escalation Strategy with Low Starting Dose in Patients with Colorectal Cancer
Presenter: Toshiki Masuishi
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3244 - Regorafenib for metastatic colorectal carcinoma: a registry-based analysis
Presenter: Katerina Kopeckova
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract