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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Presentations: 1
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
P2.13-25 - Analysis of EGFR Mutations Using Circulating Tumour DNA (ctDNA) in Non-Small Cell Lung Cancer Patients in North East Scotland (ID 13346)
16:45 - 18:00 | Presenting Author(s): Paula Scott
Treatment with 1st or 2nd generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) can benefit patients with EGFR-TKI sensitising mutations but eventually patients develop resistance. The main cause of resistance - EGFR c.2369C>T (T790M) mutation - can now be targeted using 3rd generation EGFR-TKIs. EGFR testing using ctDNA provides a minimally invasive method of mutation detection. This study aimed to:
1) Validate the Roche CE-IVD cfDNA workflow for EGFR mutation detection.
2) Assess the usefulness of monitoring patients using ctDNA EGFR testing throughout EGFR-TKI treatment, particularly to determine whether EGFR c.2369C>T resistance mutation could be detected prior to clinical progressiona9ded1e5ce5d75814730bb4caaf49419 Method
Control samples with known allele frequencies and 86 blood samples, collected from 17 patients throughout EGFR-TKI treatment, were analysed. The ctDNA was extracted using the cobas® cfDNA sample preparation kit and mutation analysis conducted by the cobas® EGFR mutation test v2. The semi-quantitative index (SQI) was used to indicate intra-patient fluctuations in mutation level between sequential samples. Mutation results were correlated with clinical status.4c3880bb027f159e801041b1021e88e8 Result
Control samples proved the method was highly sensitive, with the ability to detect a range of EGFR mutations present at 1% allele frequency, with 100% specificity. A valid result was obtained for all patient samples tested. Radiological/clinical assessment of 11/17 patients indicated progression; 6/11 (55%) displayed T790M in ctDNA which was detectable prior to clinical progression in 4 patients. Other well documented resistance mechanisms were not sought in this study. The original EGFR mutation was not detected in sequential ctDNA samples during treatment in 7 patients. Within this group, 3/7 patients continued to respond well to treatment. However, 4/7 displayed signs of clinical progression including brain metastasis only progression. The lack of mutation detection in these patients may be due to false negative results relating to inadequate ctDNA level, in particular due to the blood-brain barrier.8eea62084ca7e541d918e823422bd82e Conclusion
Analysis of controls and sequential samples obtained from patients undergoing EGFR-TKI treatment showed the technique to be sensitive and specific with the ability to detect original sensitising mutations and emergence of T790M. There is evidence that this technique can be useful in identifying the T790M mutation prior to signs of clinical progression, and that results from ctDNA generally correlate well with clinical status.6f8b794f3246b0c1e1780bb4d4d5dc53
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