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Y. Lu
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MA 06 - Lung Cancer Biology I (ID 660)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:N. Motoi, Keith M Kerr
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 501
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MA 06.09 - Detection of EGFR T790M Mutations by Four Testing Platforms in ctDNA from Chinese Patients with Advanced NSCLC (ID 8615)
15:45 - 17:30 | Author(s): Y. Lu
- Abstract
- Presentation
Background:
Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) targeting sensitizing mutations and T790M mutation, which causes ~60% of acquired resistance after first-line TKI treatment. T790M testing provides guidance for second-line treatment decisions. This study evaluated four T790M detection platforms using plasma circulating tumor DNA (ctDNA).
Method:
ADELOS is a multicentre, open-label, single-arm study (NCT 02997501) of Chinese patients with advanced non-small cell lung cancer (NSCLC) and progression on previous EGFR-TKI treatment. Plasma ctDNA testing for T790M was performed by Cobas[®] real-time polymerase chain reaction (PCR), super amplification refractory mutation system (Super-ARMS) PCR, capture-based next-generation sequencing (NGS, 168 gene panel), and QuantStudio3D digital PCR (3D dPCR). T790M-positive patients detected by these platforms received osimertinib 80 mg/day orally until progression. Matched tissue re-biopsy samples were also tested by Cobas[®] or NGS. The primary objectives were to evaluate concordance between the Cobas[®] test and the other three platforms and to assess the efficacy of osimertinib in ctDNA T790M-positive patients.
Result:
Of 256 patients enrolled, 181 were ctDNA T790M-positive, among which 167 received osimertinib monotherapy. T790M plasma positive rate was from 37.4% to 63.5% (Cobas[®]< Super-ARMSCobas[®] PCR n=254 Super-ARMS PCR n=256 NGS n=256 3D dPCR n=255 T790M detected, n (%) 95 (37.4) 108 (42.2) 138 (53.9) 162 (63.5) Comparison vs Cobas plasma test (n=254) Concordance %, (95% CI) -- 91.3 (87.2, 94.5) 82.7 (77.5, 87.1) 66.8 (60.6, 72.6) Sensitivity %, (95% CI) -- 94.7 (88.1, 98.3) 98.9 (94.3, 100.0) 90.5 (82.8, 95.6) Specificity %, (95% CI) -- 89.3 (83.4, 93.6) 73.0 (65.3, 79.7) 52.5 (44.4, 60.5) Comparison vs Tissue (n=73) Concordance %, (95% CI) 67.1 (55.1, 77.7) 64.4 (52.3, 75.3) 69.9 (58.0, 80.1) 61.6 (49.5, 72.8) Sensitivity %, (95% CI) 57.1 (42.2, 71.2) 61.2 (46.2, 74.8) 71.4 (56.7, 83.4) 69.4 (54.6, 81.7) Specificity %, (95% CI) 87.5 (67.6, 97.3) 70.8 (48.9, 87.4) 66.7 (44.7, 84.4) 45.8 (25.6, 67.2)
Conclusion:
Super-ARMS showed highest concordance and NGS showed highest sensitivity compared with Cobas® plasma T790M testing. Concordance and specificity of 3D dPCR was lower using other ctDNA tests or tissue as reference. Subsequent osimertinib treatment in these patients will justify the effectiveness of T790M testing by different technologies.
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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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P3.01-052 - The Prevalence and Genotype Distribution of Dual in Cis EGFR Mutations in Chinese Advanced Non-Small Cell Lung Cancer Patients (ID 9721)
09:30 - 16:00 | Author(s): Y. Lu
- Abstract
Background:
The prevalence of EGFR mutation has been well elucidated in different ethnicities. Recently, increasing attention has been given to dual EGFR mutations. However, less attention has been invested in dual in cis EGFR mutations. Until now, none of retrospective or prospective research has focused on dual in cis EGFR mutations except case reports.
Method:
In this real world study, we performed capture-based ultra-deep targeted sequencing on circulating tumor DNA to identify and investigate the prevalence and genotype distribution of dual in cis EGFR mutations in 3,000 Chinese advanced NSCLC patients. This cohort consisted of both treatment-naïve and previously treated patients. Ten milliliter of peripheral blood was collected from every patient and a minimum of 50ng of ctDNA was needed for library construction. The panel covered critical exons and introns of 168 genes (160kb of human genomic regions).
Result:
1,266 patients harbored EGFR mutant in this cohort; among them, 501 patients harbored 19 deletions, 489 harbored L858R, and the remaining harbored other EGFR mutations. We identified 1.5% patients (19/1,266) harboring dual in cis EGFR mutations. Among them 37% (7/19）carried two rare EGFR mutations and the remaining 63% (12/19) carried EGFR L858R in combination with a rare mutation. No patient carried EGFR 19 del in combination with other rare mutations was identified in this cohort, suggesting EGFR 19del is a stronger oncogenic driver than EGFR L858R (p=0.000197, Fisher’s exact test). For patients carried two rare mutations, both mutations were either located on exon 18 or exon 21. The allelic fractions (AF) of both mutations were similar. The AF of either EGFR mutations was the maximum AF in all patients, demonstrating the clones harboring EGFR mutations were major clones. Interestingly, 1 patient carried additional KRAS mutation and 2 patients had EGFR amplification.
Conclusion:
In cis dual EGFR mutation was rare (1.5%) in EGFR mutant Chinese advanced NSCLC patients. EGFR L858R was significantly more likely to couple with a rare in cis dual mutation than 19 del. EGFR 19del might be a stronger oncogenic driver than EGFR L858R.
