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Multicenter Study
. 2023 Jan 31:29:1610707.
doi: 10.3389/pore.2023.1610707. eCollection 2023.

FACILITATE: A real-world, multicenter, prospective study investigating the utility of a rapid, fully automated real-time PCR assay versus local reference methods for detecting epidermal growth factor receptor variants in NSCLC

Anke Behnke  1 , Anne Cayre  2 , Giovanna De Maglio  3 , Giuseppe Giannini  4 , Lionel Habran  5 , Marina Tarsitano  6 , Massimiliano Chetta  6 , David Cappellen  7 , Alexandra Lespagnol  8 , Cecile Le Naoures  9 , Gabriella Massazza  10 , Annarita Destro  11 , Irina Bonzheim  12 , Achim Rau  12 , Achim Battmann  13 , Bettina Kah  14 , Emmanuel Watkin  15 , Michael Hummel  1
Affiliations
Multicenter Study

FACILITATE: A real-world, multicenter, prospective study investigating the utility of a rapid, fully automated real-time PCR assay versus local reference methods for detecting epidermal growth factor receptor variants in NSCLC

Anke Behnke et al. Pathol Oncol Res. .

Abstract

Accurate testing for epidermal growth factor receptor (EGFR) variants is essential for informing treatment decisions in non-small cell lung cancer (NSCLC). Automated diagnostic workflows may allow more streamlined initiation of targeted treatments, where appropriate, while comprehensive variant analysis is ongoing. FACILITATE, a real-world, prospective, multicenter, European study, evaluated performance and analytical turnaround time of the Idylla™ EGFR Mutation Test compared with local reference methods. Sixteen sites obtained formalin-fixed paraffin-embedded biopsy samples with ≥ 10% neoplastic cells from patients with NSCLC. Consecutive 5 μm sections from patient samples were tested for clinically relevant NSCLC-associated EGFR variants using the Idylla™ EGFR Mutation Test and local reference methods; performance (concordance) and analytical turnaround time were compared. Between January 2019 and November 2020, 1,474 parallel analyses were conducted. Overall percentage agreement was 97.7% [n = 1,418; 95% confidence interval (CI): 96.8-98.3], positive agreement, 87.4% (n = 182; 95% CI: 81.8-91.4) and negative agreement, 99.2% (n = 1,236; 95% CI: 98.5-99.6). There were 38 (2.6%) discordant cases. Ninety percent of results were returned with an analytical turnaround time of within 1 week using the Idylla™ EGFR Mutation Test versus ∼22 days using reference methods. The Idylla™ EGFR Mutation Test performed well versus local methods and had shorter analytical turnaround time. The Idylla™ EGFR Mutation Test can thus support application of personalized medicine in NSCLC.

Keywords: DNA mutational analysis; clinical decision-making; epidermal growth factor receptor; non-small cell lung cancer; turnaround time.

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Conflict of interest statement

IB declares receipt of honoraria from Novartis, Bayer, Pfizer, Takeda, AstraZeneca and BMS. EW declares the receipt of honoraria from AstraZeneca and MSD. MH declares membership in advisory councils or committees for AstraZeneca, Roche, Novartis, Pierre Fabre GDM, Sanofi, MSD and BMS; and receipt of grants or funds from AstraZeneca. Author EW was employed by the company CYPATH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from AstraZeneca, Cambridge, UK and Biocartis, Mechelen, Belgium. Biocartis were involved in study design, and analysis and interpretation of data. AstraZeneca were not involved in study design or analysis and interpretation of data. The funders were not involved in collection of data. The funders reviewed the manuscript before submission.

Figures

FIGURE 1
FIGURE 1
FACILITATE study workflow. EGFR, epidermal growth factor receptor.
FIGURE 2
FIGURE 2
Flow chart of samples. In all cases, concordance was calculated on primary variant level (variant vs. variant). Discordant positive: variant by Idylla™ EGFR Mutation Test, no variant by reference method; discordant negative: variant by reference method, no variant by Idylla™ EGFR Mutation Test; discordant by design: rare EGFR variant not in panel of Idylla™ EGFR Mutation Test. *A total of five samples were concordant for the primary variant but discordant for secondary variant; therefore, the same five samples appear in both the concordant and discordant categories. †No results were available from the respective reference tests or the Idylla™ EGFR Mutation Test for these three samples. EGFR, epidermal growth factor receptor.
FIGURE 3
FIGURE 3
Overall cumulative percentage of tested sample results returned to the submitting clinician per aTAT: Idylla™ EGFR Mutation Test versus local reference methods. Percentage of submitted samples for which clinically actionable results were available per increasing aTAT when analyzed using the Idylla™ EGFR Mutation Test or reference methods across sites. aTAT, analytical turnaround time; EGFR, epidermal growth factor receptor.
FIGURE 4
FIGURE 4
Median aTAT determined for Idylla™ and reference methods across sites where data were available. Data for each reference method (HC-NGS and cobas®) at Site 5 were assessed as one data set (involving a total of n = 97 samples) due to low sample numbers for each method if analyzed individually. Error bars represent minimum and maximum values; box plot represents Q1, median, and Q3. aTAT, analytical turnaround time; EGFR, epidermal growth factor receptor; HC, hybrid capture; NGS, next-generation sequencing.
See this image and copyright information in PMC

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