Diaceutics reveals the data from an abstract poster discussion presentation, highlighting the readiness of molecular testing labs in EU4 to detect FGFR2 fusions in CCA clinical practice. The data was presented at ESMO Congress 2021.
Cholangiocarcinoma (CCA) is a highly heterogeneous biliary malignant tumor type, whose incidence is increasing globally; being the second most common primary hepatic malignancy after hepatocellular carcinoma. No major advances have been made over the last years in relation to patient prognosis; 1 however, early in 2021, the European Medicines Agency approved an FGFR2 inhibitor for advanced, metastatic CCA FGFR2 fusion positive patients².
In August 2020, ahead of this EMA approval, ESMO published “Recommendations for the use of Next-Generation Sequencing (NGS) for patients with metastatic cancers” ³ where NGS was recommended for daily practice to support testing of CCA tumor samples. NGS provides a means to identify multiple alterations using a single test and can be particularly useful where the paucity of tumor tissue (e.g., CCA) presents a challenge for the comprehensive detection of actionable Precision Medicine biomarkers. However, adoption of NGS technologies varies between European markets with fusion detection capabilities commonly being limited to known fusions only1.
With more FGFR2 therapies anticipated, it will be important to identify all CCA patients with any FGFR2 fusion. Therefore, Diaceutics sought to evaluate the readiness of molecular testing labs in EU4 to detect FGFR2 fusions in CCA clinical practice.
Using Diaceutics Diagnostic Network for Precision Medicine (DXRX®), 199 EU4 labs across France, Germany, Italy, and Spain were assessed for their capability to provide full coverage of FGFR2 fusions using NGS, in a clinical setting. Data was collected from January-December 2020 and included NGS testing capabilities, sample type, FGFR2 fusion testing availability and turnaround time (TAT) to reporting results.
The analysis of Diaceutics data reveals Spain has the highest number of labs (86%) capable of detecting a full range of FGFR2 fusions. In contrast, fewer French NGS labs (36%) are prepared for routine clinical FGFR2 testing, however, they provide faster TAT (10 days versus median of 11.5 days and max of 14 days in Italy). 59% and 41% of German and Italian labs, respectively, provide full FGFR2 fusion detection. All labs test using solid tissue biopsies. Uptake of liquid biopsy use varies from 77% in France to 5% in Spain.
Marianna Sciortino, PHD, Client Engagement Senior Director and co-author at Diaceutics noted that, “NGS allows labs to identify numerous alterations using a single test and has proven be incredibly useful when the size of the sample makes it challenging to detect significant Precision Medicine biomarkers. However, our research has shown that whilst there are a high number of EU4 labs currently able to perform routine clinal NGS testing on solid tumor samples, this varies significantly on a country-by-country basis, with only approximately half of the labs, currently using assays, able to detect FGFR2 alterations. This variation in performance can have a number of causes, but it has become clear from our research that more needs to be done to support EU4 labs to ensure that they are able to routinely detect relevant FGFR2 fusions in CCA patients.”
The presentation of Diaceutics’ analysis reveals gene fusion testing clinical utility is well established, and the breadth of possible actionable gene fusions (e.g., ALK, NTRK, FGFR2) in solid tumors continues to grow. NGS provides a means to identify any fusion present using a single test and is the recommended method of choice to provide simultaneous, full coverage of FGFR2 fusions where the paucity of tissue for tumors (e.g., CCA) limits PCR or FISH.
Results reveal the proportion of labs ready to provide full FGFR2 fusion detection via NGS in CCA varies across the EU4. This may reflect a possible centralized approach to NGS testing in some countries. It may also highlight a need for more labs to prepare NGS use beyond common diseases (e.g., lung cancer) to rarer conditions like CCA.
The preference towards the use of commercially available NGS assays does mean that more labs already have an existing capability to detect FGFR2 alterations. However, further analysis reveals that the high usage of targeted NGS solid tumor panels that do not commonly detect unknown FGFR2 fusions will limit the labs capabilities to support robust therapy decisions for CCA patients.
Detection capabilities for the type of FGFR2 alterations vary significantly with a minority of labs being able to detect FGFR2 fusions with unknown partners, which are a highly prevalent alteration type in CCA,5. Thus the responsibility lies with the physician to be able to recognize the limitations of the test used by the lab and interpret the laboratory report accordingly to make an informed decision regarding which FGFR2 therapeutic might be relevant for their patient
Most assays currently being used that detect FGFR2 alterations are validated for tissue samples, therefore challenges associated with sample acquisition in CCA may present a barrier for these patients getting a biomarker test result, which would then have supported them getting access to a better therapeutic option.
Diaceutics believe that whilst the capability exists in the lab cohort to perform FGFR2 fusion testing using NGS, more work needs to be done to support labs to ensure that these assays comprehensively detect relevant FGFR2 fusions and can be used to support therapeutic decisions in CCA patients.
Enabled by DXRX – The Diagnostic Network®, Diaceutics provides seamless diagnostic testing for precision medicines through deep analysis and disease level-understanding of the testing journey. Through the extraction of insights from the world’s richest repository of diagnostic testing data available via its DXRX platform, the company leverages unique proprietary Disease Diagnostic Pathways (DDPs®) to identify the best possible testing journey for patients within a specific disease or disease area.
Details of the presentation are as follows:
Assessment of EU4 laboratory readiness for FGFR2 fusion testing of cholangiocarcinoma by NGS
Authors: Marianna Sciortino PhD¹, Neil Atkey Dip RCPath¹, Brigitte Bisaro PhD¹, Gwendolyn Courtois MSc¹, Nikola Holtkamp PhD1 , Jone Iparraguirre PhD1 , Robert J Holt PhD1 , Peter V Riccelli PhD2 , Susanne Munksted MSc1 , Jordan Clark MPhil1 1 Diaceutics, Belfast, Northern Ireland, UK; 2 Diaceutics, Parsippany, NJ, US
Access to the study can be gained via: ESMO 2021 Poster Download page | Assessment of EU4 laboratory readiness for FGFR2 fusion testing of cholangiocarcinoma by NGS (diaceutics.com)
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