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
1310 - Lymphocytes express receptor tyrosine kinases in patients with renal cell carcinoma and healthy donors
Presenter: Ilya Tsimafeyeu
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
1596 - Oncogenes analysis using GO-based clustering
Presenter: Dmitriy Babenko
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
5181 - PNU-74654 enhances the antiproliferative effects of 5-FU in breast cancer and antagonizes thrombin induced cell growth via the Wnt Pathway
Presenter: Soodabeh Shahid Sales
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
3344 - P21 has the potential to become the monitoring marker for the CDK4/6 inhibitors resistance in breast cancer
Presenter: Masafumi Iida
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
894 - Overexpression of NAMPT in adult T-cell leukemia/lymphoma patients and anti-tumor activity of a NAMPT inhibitor in vivo
Presenter: Tomohiro Kozako
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
2224 - 9-ING-41, a clinically relevant inhibitor of Glycogen Synthase Kinase-3 (GSK-3), is active pre-clinically in human bladder and renal cell cancers
Presenter: Hiroo Kuroki
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
3380 - A new natural compound identified with metabolomic approach has cytotoxic activity against human colorectal cancer cell lines with acquired resistance to cetuximab
Presenter: Vincenzo De Falco
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
4713 - Multiple Myeloma Metal Levels and Proteasome Activity
Presenter: Kai Uwe Stumpf
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
4134 - A translational drug-screening tool for interrogating the effect of anti-TGF-_ therapy on fibroblast activity and the desmoplastic reaction
Presenter: Neel Nissen
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
2736 - Eribulin demonstrate selectively high sensitivity to recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) cells and xenograft tumors
Presenter: hiroko kitahara
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