Abstract 1337
Background
Standard guidelines recommend mutation testing for KRAS, NRAS and BRAF in MCRC. POG at BC Cancer is an investigational project that performs WGTA to identify potential hypothetical actionable biomarkers. We aimed to determine its clinical significance compared to standard sequencing panels by analyzing the prevalence of actionable variants and their impact on treatment decisions.
Methods
We analyzed 69 POG MCRC patients (pts) and summarized their WGTA results to identify germline and somatic coding variants, copy number alterations, structural alterations and gene expression outliers. Actionable items were defined as variants that could direct therapy with an investigational or approved agent, and were classified as either standard (found in local sequencing panel- BC Oncopanel) or expanded (not in Oncopanel).
Results
74% of pts received 2 or more prior lines of chemotherapy. 1 pt died before biopsy was made available and 1 pt had an unsuccessful biopsy. Remaining analysis of 67 pts revealed 49 (73%) pts with actionable alterations, of which 43% consisted of mutation changes, 40% expression changes, 14% copy number variants, and 3% high mutational burden or HRD. Most common standard alterations (54%) were mutations in TP53, KRAS, BRAF, PIK3CA and most common expanded items (46%) were high expression of FGFR1/3, FLT1/3, and VEGFA/B. Among these, 13 (27%) pts had alterations that led to standard chemotherapy or anti-EGFR based treatment, and 7 (14%) pts had a variant that resulted in non-standard therapies. Of those, only irbesartan, targeting the FOS-JUN pathway, resulted in a meaningful response duration of 28 months, while the remaining had an average PFS of 1.7 month. 29 (59%) pts did not receive therapy outlined in POG analysis due to lack of access for the target drug (n = 15), poor performance status (n = 7), and patient or physician preference (n = 7).
Conclusions
WGTA in MCRC provided additional understanding of tumor biology, with high rates of expression changes not otherwise captured in standard sequencing panel. However, at the present time, there is limited additional clinical therapeutic benefit in comparison. Future development is needed and ongoing.
Clinical trial identification
Legal entity responsible for the study
BC Cancer.
Funding
BC Cancer Foundation.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1978 - FAM115c that upregulates proliferation and invasion under hypoxia could be a predictive biomarker for pancreatic cancer.
Presenter: Kiyoshi Saeki
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
3682 - Pathologic assessment following neoadjuvant immunotherapy or chemotherapy demonstrates similar patterns in non-small cell lung cancer (NSCLC)
Presenter: Annikka Weissferdt
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
3319 - Tumor-infiltrating CD3+ lymphocytes and ICOS+ T-cells predict a favorable survival in resected esophageal squamous cell carcinoma
Presenter: Min Hee Hong
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
5130 - Chemokine receptor CXCR7 expression, function and clinical implications in head and neck squamous cell carcinoma
Presenter: Myung-Won Lee
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
4483 - Assessment of PD-1/PD-L1 colocalization in hepatocellular carcinoma (HCC) using bright-field double labeling and quantitative digital image analysis
Presenter: Thomas Mrowiec
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
1175 - Pulmonary tumor thrombotic microangiopathy (PTTM): 24 case series and its criteria for pathological diagnosis.
Presenter: Naoko Sato
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
1359 - Autofluorescence: a new marker for identifying cancer stem cells (CSCs) in primary tumors
Presenter: Miriam López Gómez
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
2651 - NACC1 as a target of microRNA-331-3p regulates cell proliferation in urothelial carcinoma cells
Presenter: Kohei Morita
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
2233 - Somatic-stem transition of tumor cells is a key link in the metastasis
Presenter: Nicolai Litviakov
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
2601 - Profile of individuals who never undergo colorectal cancer screening
Presenter: Jérôme Viguier
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