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L.V. Kempen
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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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P3.01-019 - Canadian Multicentre Validation Study of Plasma Circulating Tumour DNA for Epidermal Growth Factor (EGFR) T790M Testing (ID 8878)
09:30 - 09:30 | Author(s): L.V. Kempen
- Abstract
Background:
Plasma detection of EGFR T790M mutations in circulating tumour DNA (ctDNA) of advanced lung cancer patients with acquired resistance to EGFR tyrosine kinase inhibitor (TKI) has been proposed as alternative to tumor re-biopsy. This national validation study across Canadian centres aimed to establish the sensitivity and specificity of plasma detection of T790M as a clinical test using digital droplet (dd)PCR and next generation sequencing (NGS) assays.
Method:
Canadian patients at 7 centres undergoing screening for ASTRIS (NCT02474355) were invited to participate in this companion blood-based study. Patients with acquired resistance to EGFR TKI consented to collection of blood samples and demographic data. Samples were analysed using ddPCR and/or NGS platforms available at 4 molecular diagnostic laboratories across Canada. Concordance between the results of plasma T790M assayed in these 4 laboratories with reference tissue/plasma testing conducted for ASTRIS was assessed.
Result:
63 patients participated; the median age was 64 years (range 31-87), 69%(40/58) were Asian; 55%(33/60) were male. All patients received prior EGFR TKI, 17%(10/60) also received prior chemotherapy. Reference testing for EGFR T790M for ASTRIS eligibility identified positive T790M(+) results for 31(49%), negative(-) for 30(48%) and indeterminate(i) results for 2(3%) patients. One laboratory tested all 63 patient samples using both ddPCR and NGS (Oncomine Lung cfDNA assay), another laboratory tested 18 samples using ddPCR and NextSeq, a third tested 10 samples using ddPCR and COBAS EGFRv2, and a fourth tested 6 samples using Ion Torrent PGM. A total of 188 tests were performed including 91 by ddPCR, 87 NGS and 10 COBAS assays. Combining test results for each patient, 60%(38/63) of patient plasma samples were T790M+, 23(37%) were T790M-, and 2(3%) were inconclusive. Of 31 patients with reference T790M+ results from ASTRIS, 23(74%) had T790M detected in plasma, 6(19%) did not (T790M-), and 2(7%) had indeterminate (T790Mi) plasma results. For 30 patients with T790M- reference results from ASTRIS, 13(43%) had plasma T790M+ and 17 plasma T790M- results. The 2 patients with T790Mi by reference testing both had T790M+ results from plasma. Altogether, 47%(15/32) of patients deemed to have T790M-/i tumours by reference testing were found to have T790M+ results by plasma in this multicentre study. Combining results from both tissue and plasma testing, 73%(46/63) of study patients had T790M+ results.
Conclusion:
Plasma ctDNA testing in this multicentre Canadian study identified a significant number of additional patients eligible for osimertinib therapy beyond routine biopsy tissue testing for EGFR T790M.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-097c - Detection of the EGFR P.(T790M) Mutation by Different Methods: A Small Comparison Case Study (ID 10260)
09:30 - 09:30 | Author(s): L.V. Kempen
- Abstract
Background:
About 50-60% of non-small cell lung cancer (NSCLC) patients with a Tyrosine Kinase Inhibitor (TKI) sensitizing EGFR mutation can develop therapy resistance via the acquisition of the additional p.(T790M) mutation. The identification of this group of patients is important because they can be treated with a 3[rd] line TKI: Osimertinib. Analysis of plasma samples has become a minimally invasive alternative to repeat tissue biopsy for the detection of the EGFR p.(T790M) mutation. The mutation can be detected in plasma and tissue by various methods including the FDA approved Roche COBAS® EGFR v2 test, the EntroGen® EGFR test and digital droplet PCR (ddPCR). In this study, we compared the detection of the EGFR p.(T790M) mutation by ddPCR and COBAS in plasma specimens, and ddPCR and EntroGen in tissue specimens.
Method:
Blood from 14 NSCLC was collected in STRECK™ blood collection tubes. Plasma was prepared and circulating cell-free (ccf) DNA extracted with the COBAS and Qiagen method. DNA was analyzed for the presence of the EGFR TKI sensitizing and p.(T790M) mutation by COBAS, or the p.(T790M) mutation only by ddPCR on a Biorad QX200 platform. In addition, 26 biopsies from EGFR-positive patients who progressed on TKI, and which were tested p.(T790M) negative by Entrogen were re-analyzed by ddPCR.
Result:
Nine out of fourteen plasma samples were found to contain DNA with the sensitizing EGFR mutation by COBAS. The p.(T790M) mutation was found in four of these nine cases. ddPCR revealed one additional p.(T790M)-positive plasma sample that was tested negative by COBAS. ddPCR detected ten p.(T790M)-positive cases in the 26 EntroGen p.(T790M) negative samples, and suggests a 38% of false negative rate of the EntroGen method in this small cohort of samples.
Conclusion:
ddPCR for the detection of the EGFR p.(T790M) mutation in plasma and tissue appears to be associated with a higher sensitivity compared to the COBAS and EntroGen methods, respectively.
