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Dongsheng Yue
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-26 - Uncommon EGFR Mutations Sensitive to First-Generation EGFR-TKI, Icotinib (Now Available) (ID 2091)
08:00 - 18:00 | Presenting Author(s): Dongsheng Yue
- Abstract
Background
The first-generation EGFR-TKIs are the standard of care for non-small cell lung cancer patients withEGFR activating mutations. Patients with EGFR L858R (p.L858R) or exon 19 deletions are the most prevalent subgroup sensitive to EGFR-TKIs. Previous reports showed that the minority of lung cancer patients with rare EGFR mutations still achieved clinical benefit with EGFR-TKIs. Here, we profiled the landscape of gene mutations in lung cancer patients who responded to Icotinib (a first- generation EGFR-TKI approved in China) treatment without classic EGFR activating mutations.
Method
We performed a comprehensive sequencing study by a NGS-based panel on a cohort of eleven lung adenocarcinoma patients without common EGFR sensitive mutations and receiving Icotinib treatment in a previous clinical trial (ICOGEN, NCT01040780). The pre-treatment FFPE tissues from all eleven patients were sequenced using a 500-gene panel.
Result
Six patients responded to Icotinib treatment including three patients with partial response (PR) and three patients with stable disease (SD). The other five patients showed immediate disease progression (PD) after the treatment of Icotinib. Rare EGFR mutations in the EGFR tyrosine kinase domain , including EGFR mutations W731C (exon 19), M793I (exon 20), and V845L (exon 21), were detected in the PR and SD groups but not in the PD group. EGFR somatic mutation M793I has been detected in the lung tissue of a patient according to the COSMIC record (COSM1716335). In the PR and SD groups, ERBB2 I655V and JAK2 R215Q were identified as potential mutations which could relate to Icotinib sensitivity.
Conclusion
This study uncovered potential new biomarkers predicting the clinical benefit to Icotinib. With further validation and evidence, it may expand the current patient populations which benefits from the first-generation EGFR-TKIs.
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P2.11 - Screening and Early Detection (ID 178)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.11-15 - Detection of Circulating Genetically Abnormal Cells Improves the Diagnostic Accuracy in Lung Cancer Presenting with GGNs (ID 1533)
10:15 - 18:15 | Author(s): Dongsheng Yue
- Abstract
Background
Popularization of low-dose computed tomography (LDCT) screening enables more finding of pulmonary ground glass nodules (GGNs). It remains a challenge for distinguishing between malignant and benign nodules in patients with size ≤30mm GGNs depending on CT. Moreover, serum tumor markers showed poor prediction value. There is an urgent need to develop a noninvasive and highly accurate biomarker for detection. Recent studies have suggested that circulating genetically abnormal cells (CACs) can be identified by fluorescence in situ hybridization (FISH) from peripheral blood of early-stage lung cancer in Caucasian. This study aimed to use CACs to improve the diagnostic accuracy of early-stage lung cancer with GGNs in Chinese population.
Method
Peripheral blood was collected from 107 patients with GGNs and 55 healthy donors. All GGNs identified by CT were between 5-30mm in diameter and confirmed with histopathological diagnosis after surgical resection. The level of serum-based biomarkers (CEA, NSE, TPSA, SCC, PROGRP, CA19-9 and CYFRA21-1) were measured. CACs were enriched by density gradient separation, and visualized by 3p22.1, 3q29, 10q22.3, CEP10 FISH. CACs were identified by finding gains in two or more probes.
Result
Of these 107 GGNs, 96 were malignant (45 pure GGNs and 51 mixed GGNs) and 11 were Benign. All malignant GGNs were stage I lung adenocarcinomas. CACs were detected in 68 of 96 lung cancers, while serum-based biomarkers were just positive in 39 of those. The sensitivity, specificity of CACs test were 70.8%, 77.3% respectively for this cohort (96 malignant GGNs, 11 benign GGNs and 55 healthy donors). The area under the receiver operating characteristic (ROC) curve was 0.760 from this data set. There was no significant difference in CACs test sensitivity between GGNs size of <20mm and ≥20mm (71.3% vs 68.8%, p=0.84). Comparing to serum-based biomarkers, the sensitivity of CACs test was significantly improved. Combining the CACs test results with serum-based biomarkers, the overall sensitivity increased to 77.1% without lowering specificity.
Sensitivity on malignant GGNs (N=96) Sensitivity on malignant pure GGNs (N=45) Sensitivity on malignant mixed GGNs (N=51) CACs 70.8% 68.9% 72.5% serum-based biomarkers 40.6% 40.0% 41.2% Sig. P<0.05 P<0.05 P<0.05
Conclusion
Our study showed that using CACs as a noninvasive malignant biomarker could improve the diagnostic accuracy in early-stage lung cancer presenting with GGNs.
