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Found 3 Presentations For Request "idylla"
1205P - FACILITATE: A real-world multicentre prospective study investigating the utility of a rapid, fully automated RT-PCR assay vs reference methods (RM) for detecting epidermal growth factor receptor mutations (EGFRm) in NSCLC
- Michael Hummel (Berlin, Germany)
Abstract
Background
Rapid and accurate EGFRm testing is essential to inform treatment decisions for patients with advanced NSCLC. A fully automated, rapid EGFRm diagnostic workflow may decrease turnaround time, allowing faster treatment initiation. This prospective study evaluated the performance and analytical turnaround time (aTAT) of the Idylla™ EGFR Mutation Test, compared with local RM in several real-life workflows.
Methods
Sixteen sites in Belgium, France, Germany and Italy aimed to prospectively test 100 paraffin-embedded biopsy or cytologic tissue samples with ≥10% neoplastic cells from patients with advanced NSCLC. Consecutive sample sections were parallel tested using Idylla™ (5 μm section) and a local RM. RM were targeted next-generation sequencing (NGS, different gene panels), Cobas® EGFR Mutation Test, Sanger sequencing, Pyrosequencing, Sequenom mass spectrometry, Hybrid Capture and Entrogen EGFR Mutation Analysis Kit. Key endpoints were Idylla™ concordance with RM and aTAT (time between lab receipt of sample and result ready by diagnostic test).
Results
To date, data have been collected from 13 sites (n=1245 samples). The overall percent agreement (OPA) for EGFRm detection between Idylla™ and RM (n=1192 valid tests) was 97%, with a positive PA of 87% and a negative PA of 99%. Of the 3% discordances between Idylla™ and RM, 49% were discordant negative (of which 38% were T790M discordant), 27% discordant positive and 24% rare EGFRm that Idylla™ is not designed to detect. 90% of all samples were tested in ≤7 days using the Idylla™ method vs ≤21 days using RM. Differences in mean (±standard deviation) aTAT were observed between RM used, ranging from 4 ±2 days (mass spectrometry) to 23 ±7 days (outsourced NGS). The mean Idylla™ aTAT range between sites was 1 ±1 to 8 ±7 days.
Conclusions
This large, prospective, multi-centre, real-world data set confirms that Idylla™ offers a high OPA and specificity for detecting EGFRm in NSCLC tumour samples vs RM. Idylla™ could be used for a range of lab needs, for example improving aTAT, supporting institutions that do not have access to advanced molecular testing, or use in fast-track testing.
Editorial acknowledgement
We thank Robert Harrison, PhD, from iMed Comms, who provided medical writing support funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca and Biocartis.
Disclosure
M. Hummel: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: F. Hoffmann-La Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre. G. De Maglio: Research grant/Funding (institution): AstraZeneca. E. Watkin: Honoraria (institution), Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: BMS. All other authors have declared no conflicts of interest.
32P - Comparison of fully automated microsatellite instability test to immunohistochemistry for mismatch repair protein expression in endometrial carcinoma
- Marta Mendiola (Madrid, Spain)
Abstract
Background
Endometrial cancer (EC) is the most prevalent amongst gynaecological malignancies, and microsatellite instability (MSI), has been reported in up to 30% of cases. This is mainly caused by alteration of DNA mismatch repair (MMR) genes and can be explored by loss of MMR proteins expression by immunohistochemistry (IHC), or alternatively, by MSI status.
Methods
Firstly, 276 early stage low grade (G1-G2) EC patients were classified by IHC by evaluation of tissue microarrays. Based on the expression of MLH1, PMS2, MSH2 and MSH6, samples were classified as MMR-proficient (MMR-p; all four proteins retained expression) or deficient (MMR-d; one or more proteins showed loss of expression). Secondly, the Idylla™ MSI Test (Idylla™), was used to retest DNA from all MMR-d cases and a random selection of an approximately equal number of MMR-p cases. Non-informative cases by IHC were also retested by Idylla™.
Results
A total of 276 EC were analysed by IHC; 30 (11%) samples were not initially informative, 35 (13%) samples were classified as MMR-d, and 211 (77%) as MMR-p. Idylla™ was able to rescue 29/30 (97%) of the non-informative IHC samples. 23/29 (79%) were determined as Microsatellite Stable (MSS) and 6/29 (21%) as MSI-High (MSI-H). In the MMR-d group, 16 out of 35 samples were equally classified, but the other 19 were classified as MSS, showing a discrete sensitivity compared to IHC (45.71%). Within the 44 MMR-p randomly selected samples, all were identically classified by Idylla™ except one, that was classified as MSI-H by Idylla™, showing high specificity compared to IHC (97.72%). Overall, there is a concordance of 74.68% between IHC and Idylla™.
Conclusions
This preliminary data show that the Idylla™ MSI Test is able to rescue the majority of samples which are classified as non-informative using IHC and that the Idylla™ MSI Test seems to be highly correlated with IHC in the identification of MMR-p EC cases, but a substantial lower concordance rate has been observed for the MMR-d EC cases. Further analyses have to be performed to explain the observed discordances of these MMR-d cases.
Legal entity responsible for the study
Hospital Universitario la Paz-IdiPAZ.
Funding
Biocartis NV.
Disclosure
M. Mendiola: Non-remunerated activity/ies, research collaboration: Biocartis; Honoraria (self), speaker: AstraZeneca; Honoraria (self), speaker: Tesaro. A. Gallego Martínez: Advisory/Consultancy: Pharmamar; Travel/Accommodation/Expenses: Pharmamar; Speaker Bureau/Expert testimony: Clovis; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: MSD; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Tesaro (GSK); Travel/Accommodation/Expenses: Pierre-Fabre; Non-remunerated activity/ies, Non remunerated membership: SEOM; Non-remunerated activity/ies, Non remunerated membership: GEICO; Non-remunerated activity/ies, Non remunerated membership: European Orgnisation Treatment Throphoblastic disease; Non-remunerated activity/ies, Non remunerated membership: ESMO. D. Hardisson: Non-remunerated activity/ies, Principal investigator, Molecular Pathology and Therapeutic Targets Lab: IdiPAZ. A. Redondo: Honoraria (self), Research grant/Funding (self), speaker and advisory role: Roche; Honoraria (self), Research grant/Funding (institution), speaker and advisory role: Pharmamar; Honoraria (self), speaker and advisory role: AstraZeneca; Honoraria (self), speaker and advisory role: GSK; Honoraria (self), speaker and advisory role: Clovis; Honoraria (self), speaker: Novartis; Honoraria (self), Advisory role: Amgen; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Eisai; Non-remunerated activity/ies, Member of executive board and secretary: GEICO; Non-remunerated activity/ies, PI of phase II Cecilia study sponsored by Roche: Roche. All other authors have declared no conflicts of interest.
461P - Real-time PCR-based assessment of RAS/BRAF mutations in the plasma of metastatic colorectal cancer (mCRC) patients: A single institution experience
- Pietro Paolo Vitiello (Napoli, Italy)
Abstract
Background
Tumour heterogeneity represents a possible source of error in detecting predictive genetic alterations in tumour tissue and can be overcome by testing for alterations in circulating tumour DNA (ctDNA) using liquid biopsy.
Methods
108 patients with a diagnosis of metastatic colorectal cancer (mCRC) were assessed for the presence of RAS/BRAF mutations in ctDNA in our Oncology Unit. Patients were divided in two cohorts: 53 patients assessed before treatment initiation (basal cohort) and 55 patients assessed after anti-EGFR treatment (post-EGFR cohort). KRAS, NRAS and BRAF mutation analysis in plasma was performed using a fully automated real time PCR-based platform (Idylla™ Biocartis). We evaluated the performance of this technique compared to tissue analysis and correlated the results to patients’ clinical features.
Results
The overall agreement between tissue analysis and liquid biopsy in the basal cohort was 81.13%, with a higher concordance in patients with liver metastases (88.57%). In patients with liver metastases, sensitivity, specificity, and positive predictive value (PPV) of liquid biopsy were 84.21%, 93.75%, and 94.12%, respectively. Circulating mutational fraction (CMF) for KRAS was significantly higher in patients with liver metastases. In one case of metachronous metastases, the detection of a RAS mutation in plasma but not on tissue analysis predicted the lack of response to anti-EGFR treatment. In the post-EGFR cohort, 13/55 patients presented detectable mutations in KRAS (9 cases), NRAS (3 cases) or BRAF (1 case) in plasma. Among the KRAS mutants, the prevalence of non-exon2 mutations was higher in the post-EGFR cohort (44%) compared to the basal cohort (21%). CMF values for KRAS increased significantly (
Conclusions
Real time PCR-based testing of RAS/BRAF mutations in plasma is feasible and reliable in mCRC patients in a clinical setting. Liver involvement increases the reliability of the technique. Plasma detection of RAS mutations has a strong clinical value in case of metachronous metastatic disease. Liquid biopsy is useful to monitor the onset and fluctuations of RAS mutations in patients receiving anti-EGFR therapy.
Legal entity responsible for the study
The authors.
Funding
Università della Campania \"Luigi Vanvitelli\".
Disclosure
P.P. Vitiello: Advisory/Consultancy: Biocartis. T. Troiani: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi. F. Ciardiello: Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: Symphogen; Advisory/Consultancy: Pfizer; Research grant/Funding (institution): Ipsen. E. Martinelli: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Merck; Advisory/Consultancy: Roche; Advisory/Consultancy: Servier; Advisory/Consultancy: Sanofi. All other authors have declared no conflicts of interest.