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Estela Sánchez Herrero
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P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.03-15 - Non-Invasive Detection of Secondary Resistance Mutations in ALK-Positive NSCLC Patients by Next-Generation Sequencing (ID 1658)
09:45 - 18:00 | Author(s): Estela Sánchez Herrero
- Abstract
Background
ALK inhibitors have led to important improvements in ALK-positive non-small cell lung cancer (NSCLC) patient’s survival and quality of life. However, despite the good responses, resistance mutations inevitably emerge. Several resistance mutations in ALK domain have been describe. Remarkably different mutations can confer different sensitivities to different ALK inhibitors. However, 2nd and 3rd line treatment is often prescribe empirically without knowing the molecular mechanism underlying treatment failure.
Method
21 samples from ALK-positive NSCLC patients were collected at disease progression. Circulating Nucleic Acids were isolated from platelets, exosomes and plasma. Libraries were prepared using 20ng of template and Oncomine™ Pan-Cancer Cell-Free Assay. Samples were sequenced on an Ion GeneStudio S5 Plus System. Sequencing data was first analyzed using Torrent Suite software. Subsequently variant calling, annotation and filtering was performed on the Ion Reporter (v5.10) platform using the Oncomine TagSeq Pan-Cancer Liquid Biopsy w2.1 workflow.
Result
In 14 (67%) patients a somatic mutation was identified in the plasma sample collected at disease progression. The average number of mutations detected per sample was 2.6. Noteworthy, 14 mutations were found in oncogenes that have been previously associated with ALK inhibitors resistance (5 mutations in ALK locus, 4 mutations in PIK3CA, 1 mutation in EGFR, 1 mutation in KIT, 1 mutation in KRAS, 1 mutation in MTOR and 1 mutation in MYC). The rest of mutations (N=21) were found in TP53 gene. Secondary resistance mutation in ALK locus occurred in 24% of the cases. Specifically, p.G1269A (N=2), p.G1202E (N=1), p.R1275Q (N=1) mutations were found in ALK-positive NSCLC who had progressed on crizotinib and p.G1202R mutation was found in 1 ALK-positive NSCLC who had progressed on ceritinib.
Conclusion
Secondary ALK-TKI resistance mutations could be detected using liquid biopsies in a high proportion of patients. Non-invasive molecular profiling of samples collected at disease progression is feasible being useful for further treatment selection in ALK-positive NSCLC patients.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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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): Estela Sánchez Herrero
- 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
