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A.M. Rachiglio
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-068 - Investigation of Low Plasma/Tissue EGFR Concordance in Russia: Follow-up to the IGNITE Global Diagnostic Study (ID 10446)
09:30 - 09:30 | Author(s): A.M. Rachiglio
- Abstract
Background:
IGNITE was a large multi-national, non-comparative, non-interventional diagnostic study whose objective was to in part determine the concordance in EGFR mutation status between tissue/cytology and plasma testing in the real world setting[1]. Locally advanced or metastatic NSCLC patients were enrolled from 9 countries in Asia-Pacific including Russia. A very significant difference was observed in performance of plasma testing in Russia (PPV=39.3%) vs. Asia Pac (PPV=92.5%) vs tissue results with only 51/84 ctDNA EGFR mutation positive results from Russian labs confirmed by the corresponding tissue result. No single lab appeared to contribute predominantly to the questionable overall performance. 1. Han, B et al.; ‘Determining the prevalence of EGFR mutations in Asian and Russian patients (pts) with advanced non-small-cell lung cancer (aNSCLC) of adenocarcinoma (ADC) and non-ADC histology: IGNITE study’ (ELCC 2015 Abstract No. 96O).
Method:
142 of the 941 evaluable plasma samples from Russia were selected to include originally discordant samples and a similar number of concordant positive and concordant negative samples. All samples were shipped to an experienced lab and re-tested for TKI sensitizing mutations using the QIAamp Circulating Nucleic Acid Kit and the Therascreen® EGFR Plasma RGQ PCR test (Qiagen). The central laboratory was blinded to the origin of the samples and original EGFR mutation result.
Result:
Adhering to package insert defined criteria for the internal control, 38 of 112 (34%) of cases were re-classified (19 to pos. and 19 to neg.). By independent clinical laboratory interpretation of the results, 55 of 142 (39%) cases were re-classified (25 to pos. and 30 to neg.). A marked improvement was seen in concordance with the local tissue result after re-testing from 38% to 69% with the false positive rate decreasing from 18.8% to 3.6%. Re-classification of 17 (81%) original ‘false positive’ and 17 (35 %) original ‘false negative’ plasma results validates the original tissue results and appropriate collection and handling of plasma.
Conclusion:
Low concordance between original tissue and plasma EGFR status for the TKI sensitizing mutations observed in the Russian cohort from the IGNITE study was primarily due analytical issues in plasma test methodology. The contribution of the specific analytical process (extraction, testing or analysis) could not be determined. This follow-up study has been communicated back to the Russian laboratories resulting in the appropriate validation and proficiency programs being put in place to ensure quality plasma EGFR ctDNA testing.
