19P Deciphering the role of precision oncology in the treatment of biliary tract cancer in daily routine practice: Retrospective analysis from the cancer center Upper Austria

Abstract

BackgroundThe routine therapeutic landscape of metastatic CCC is still largely based on cytotoxic chemotherapy. This standard gets increasingly challenged with the advent of next generation sequencing (NGS) in routine practice and evolving trials of targeted therapies in CCC. However the value of comprehensive genetic profiling of CCC in actual routine clinical practice remains poorly characterized.MethodsWe performed a retrospective study at the clinical cancer center of Upper Austria (Tumorzentrum Oberösterreich) in 2018-2021. Tumor samples from 56 patients with advanced CCC underwent comprehensive genetic profiling. TruSight Tumor 170 Assay (Illumina), Archer FusionPlex Panel (ArcherDX), Oncomine Focus Assay (Thermo Fisher Scientific) were used for NGS analysis. Furthermore MSI status was determined by custom made Multiplex PCR-Based Methods. Immunhistochemistry (IHC) collected data on Her2neu and PDL-1expression.ResultsA potentially actionable pathogenic variant was identified in 32 patients (57%). Pathogenic variants were ranked according ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). In 15 patients with ESCAT I-III criteria a molecular informed therapy was established targeting 8 FGFR alterations, 2 MSI high status, 1 Pi3kinase mutation, 2 BRCA1/2 mutations, 2 BRAF V600Emutations. In 13 of the 15 treated patients we could observe a favorable PFS2 (targeted therapy)/PFS1 (previous standard therapy) ratio >1,3, suggesting clinical benefit. Overall survival in patients receiving molecular matched therapy showed a positive trend compared to patients remaining on standard treatment protocol.ConclusionsWe could show that comprehensive molecular characterization of advanced CCC during routine clinical care leads to favorable PFS2/PFS1 ratios and probable positive overall survival. This underscores the recent ESMO recommendations for NGS reflex testing in advanced CCC.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. BackgroundThe routine therapeutic landscape of metastatic CCC is still largely based on cytotoxic chemotherapy. This standard gets increasingly challenged with the advent of next generation sequencing (NGS) in routine practice and evolving trials of targeted therapies in CCC. However the value of comprehensive genetic profiling of CCC in actual routine clinical practice remains poorly characterized. The routine therapeutic landscape of metastatic CCC is still largely based on cytotoxic chemotherapy. This standard gets increasingly challenged with the advent of next generation sequencing (NGS) in routine practice and evolving trials of targeted therapies in CCC. However the value of comprehensive genetic profiling of CCC in actual routine clinical practice remains poorly characterized. MethodsWe performed a retrospective study at the clinical cancer center of Upper Austria (Tumorzentrum Oberösterreich) in 2018-2021. Tumor samples from 56 patients with advanced CCC underwent comprehensive genetic profiling. TruSight Tumor 170 Assay (Illumina), Archer FusionPlex Panel (ArcherDX), Oncomine Focus Assay (Thermo Fisher Scientific) were used for NGS analysis. Furthermore MSI status was determined by custom made Multiplex PCR-Based Methods. Immunhistochemistry (IHC) collected data on Her2neu and PDL-1expression. We performed a retrospective study at the clinical cancer center of Upper Austria (Tumorzentrum Oberösterreich) in 2018-2021. Tumor samples from 56 patients with advanced CCC underwent comprehensive genetic profiling. TruSight Tumor 170 Assay (Illumina), Archer FusionPlex Panel (ArcherDX), Oncomine Focus Assay (Thermo Fisher Scientific) were used for NGS analysis. Furthermore MSI status was determined by custom made Multiplex PCR-Based Methods. Immunhistochemistry (IHC) collected data on Her2neu and PDL-1expression. ResultsA potentially actionable pathogenic variant was identified in 32 patients (57%). Pathogenic variants were ranked according ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). In 15 patients with ESCAT I-III criteria a molecular informed therapy was established targeting 8 FGFR alterations, 2 MSI high status, 1 Pi3kinase mutation, 2 BRCA1/2 mutations, 2 BRAF V600Emutations. In 13 of the 15 treated patients we could observe a favorable PFS2 (targeted therapy)/PFS1 (previous standard therapy) ratio >1,3, suggesting clinical benefit. Overall survival in patients receiving molecular matched therapy showed a positive trend compared to patients remaining on standard treatment protocol. A potentially actionable pathogenic variant was identified in 32 patients (57%). Pathogenic variants were ranked according ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). In 15 patients with ESCAT I-III criteria a molecular informed therapy was established targeting 8 FGFR alterations, 2 MSI high status, 1 Pi3kinase mutation, 2 BRCA1/2 mutations, 2 BRAF V600Emutations. In 13 of the 15 treated patients we could observe a favorable PFS2 (targeted therapy)/PFS1 (previous standard therapy) ratio >1,3, suggesting clinical benefit. Overall survival in patients receiving molecular matched therapy showed a positive trend compared to patients remaining on standard treatment protocol. ConclusionsWe could show that comprehensive molecular characterization of advanced CCC during routine clinical care leads to favorable PFS2/PFS1 ratios and probable positive overall survival. This underscores the recent ESMO recommendations for NGS reflex testing in advanced CCC. We could show that comprehensive molecular characterization of advanced CCC during routine clinical care leads to favorable PFS2/PFS1 ratios and probable positive overall survival. This underscores the recent ESMO recommendations for NGS reflex testing in advanced CCC.