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Carlos Garcia Giron
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-16 - Agreement Between Different Methodologies for Non-Invasive p.T790M and EGFR Sensitizing Mutation Testing (ID 1965)
10:15 - 18:15 | Author(s): Carlos Garcia Giron
- Abstract
Background
Tyrosine kinase inhibitors (TKIs) are the current standard of care for patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, most patients progressed within 1 to 2 years. The EGFR p.T790M mutation is the most common resistance mechanism to first and second generation EGFR TKIs. The identification of p.T790M mutation is of considerable clinical relevance as osimertinib has demonstrated clinical efficacy in this setting. Guidelines recommend testing for the p.T790M mutation in blood at relapse to TKIs, and re-biopsy only in case of a negative result. Several blood based methodologies for detection of EGFR mutations have been developed in the recent years. However, the number of comparison studies between platforms is very limited.
Method
This is a multicenter, cross-sectional study (ClinicalTrials.gov Identifier: NCT03363139) performed by the Spanish Lung Cancer Group. Samples from 75 consecutive EGFR mutant NSCLC patients were collected at disease progression to first line TKI treatment. The presence of EGFR mutations in the cfDNA was evaluated in 39 samples by 7 methodologies, namely: Cobas® EGFR Mutation Test v2 (Roche Diagnostics), Therascreen EGFR Plasma RGQ PCR Kit (Qiagen), QuantStudio® 3D Digital PCR System (Thermofisher), a 5′-nuclease real-time PCR (TaqMan®) assay in presence of PNA, OncoBEAM EGFR (Sysmex Inostics), NGS with two different gene panels: Oncomine® (Thermofisher) and Lung Cancer Panel (Qiagen). The agreement between methodologies was assessed using the kappa coefficient (K) and its corresponding 95% confidence intervals (95% CI). For quantitative variables the concordance correlation coefficient (ccc) was used.
Result
Complete results are available for 39 patients. Overall, the agreement between all methodologies for the detection of p.T790M mutation as well as the original EGFR sensitizing mutation was good (K=0.669; 95CI: 0.504-0.835 and K=0.750 95CI: 0.599-0.899 respectively). Remarkably, the agreement between FDA-approved methodologies for p.T790M detection was almost perfect (K=0.926; 95CI: 0.712-1) and good for the EGFR sensitizing mutations (K=0.657; 95CI: 0.417-0.902). Similarly, the agreement between NGS-based methodologies for the detection of p.T790M and the EGFR activating mutations was very high (K=0.843; 95CI: 0.567-1 and K=0.872 95CI: 0.595-1 respectively). Moreover, concordance between both technologies for p.T790M and EGFR sensitizing mutation mutant allele frequency was excellent (ccc=0.956; 95CI: 0.906-1 and ccc=0.980 95CI: 0.950-1 respectively). The proportion of samples that were positive for p.T790M detection varied from 28% (PCR based technologies) to 37% depending on the methodology.
Conclusion
NGS and PCR-based methodologies show a good to excellent agreement for the detection of EGFR mutations, including the p.T790M. Our results support the use of liquid biopsies for non-invasive testing of clinically relevant mutations (Data from the whole cohort will be presented at the meeting).
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P2.03-33 - ctDNA Levels Significantly Predicts Survival in NSCLC Patients with an EGFR Activating Mutation (ID 2016)
10:15 - 18:15 | Author(s): Carlos Garcia Giron
- Abstract
Background
Circulating tumor DNA (ctDNA) have been shown to be useful for non-invasive biomarker testing in non-small cell lung cancer (NSCLC). In addition, there is growing evidence supporting that ctDNA levels can be useful for tumor response to treatment monitoring. Nevertheless, data from large prospective clinical longitudinal studies still limited.
Method
300 plasma samples from 100 advanced NSCLC patients, with tumors harboring an EGFR activating mutation and treated with a first line tyrosine Kinase inhibitor were analyzed. Samples were collected before the start of treatment, at first follow up evaluation, at 7 month and at disease progression. ctDNA was analyzed by dPCR.
Result
Median follow up was 11.3 months. There were not significant differences in progression free survival (PFS) or overall survival (OS) according to treatment (erlotinib, afatinib or gefitinib). Patients harboring a deletion in exon 19 or a mutation in exon 21 exhibited better survival than those with an insertion in exon 20 (P<0.001). dPCR detected EGFR sensitizing mutation in 77% of the pre-treatment samples. ctDNA levels before the start of the treatment did not significantly predict survival, although a tendency was observed, with patients with high levels of ctDNA showing poorer outcome. On the contrary, patients in which the EGFR sensitizing mutation was undetectable at first follow up had a markedly better PFS and OS (HR=2.7; 95IC= 1.4-5.5 and HR= 5.5 95IC: 1.8-17 respectively). In the same way, patients in which the EGFR sensitizing mutation remained negative at 7months had a significantly increased PFS (HR: 2.8; 95IC: 1.2-6.6). None of the patients with undetectable levels at 7 months has deceased.
Conclusion
ctDNA levels is of prognostic significance in EGFR positive NSCLC patients with advance disease and can be useful to monitor treatment outcome
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P2.05 - Interventional Diagnostic/Pulmonology (ID 168)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Interventional Diagnostics/Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.05-10 - Liquid Biopsy: Association Between the Burden of Disease in Patients with EGFR-Mutated NSCLC and the Frequency of Its Detection in Blood (ID 2384)
10:15 - 18:15 | Author(s): Carlos Garcia Giron
- Abstract
Background
In the management of patient’s whit non small cell lung cancer (NSCLC) with EGFR mutations after progression to first and second generation tyrosine kinasa inhibitors (TKI), the mechanism of resistance is very important. Our objective is to analyse the appearance kinetics of the T790M by means of digital PCR techniques in liquid biopsy.
Method
We conducted a multicenter study with 100 patients with EGFR-mutated NSCLC, treated with first-line TKI therapy. We analyze the ctDNA by dPCR before the start of treatment, at first follow up evaluation, at 6 months and at disease progression.
Result
We included a total of 100 patients from July 2016 to December of 2017. Seven patients with Exon 20 insertion in EGFR were excluded (final sample 93). The median of follow-up was 12 months. There were not significant differences in progression free survival (PFS) or overall survival (OS) according to treatment (erlotinib, gefitinib or afatinib). dPCR detected EGFR sensitizing mutation in 77% of the pre-treatment samples. Of these cases, EGFR sensitizing mutation was detected in 75% of the patients with stage IVA and 85% in stage IVB respectively, p=0,075. The resistance mutation p.T790M was detected in 52% of the samples collected at disease progression. The probability to detect the resistance mutation p.T790M by liquid biopsy, is greater if the pre-treatment sample was positive for EGFR sensitizing mutation (11% vs 62%) p 0,009. In cases with progression of the disease the percent of detection of p.T790M was 52% and 54% in patients with Exon 19 deletion and L858R mutation respectively. The OS in patients with progression of the disease and p.T790M negative was 85% at 12 months (95%CI: 60%-94%) and 75% with p.T790M positive (95%CI: 49%-88%), p=0,01.
Conclusion
The burden of disease in patients with NSCLC mutated with EGFR is related to the appearance of sensitivity and resistance mutations in liquid biopsy. The probability to detect the resistance mutation p.T790M in blood, is greater if the pre-treatment sample was positive for EGFR sensitizing mutation.
