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Y.-. Wu
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MINI 03 - PD1 Axis Inhibition and EGFR (ID 101)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:L. Gandhi, Y. Ohe
- Coordinates: 9/07/2015, 16:45 - 18:15, Four Seasons Ballroom F1+F2
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MINI03.09 - Role of T790M Mutation in EGFR-TKI Rechallenge for Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (ID 1031)
17:35 - 17:40 | Author(s): Y.-. Wu
- Abstract
- Presentation
Background:
Epidermal growth factor receptor (EGFR) exon 20 T790M mutation may have a predictive role before EGFR-tyrosine kinase inhibitors (TKIs) treatment and it also might have a prognostic role after acquired resistance to EGFR-TKIs. However, its role in EGFR-TKI rechallenge after failure of initial EGFR-TKIs in EGFR-mutant advanced non-small cell lung cancer (NSCLC) remains unknown.
Methods:
We retrospectively evaluated the clinical course of 515 EGFR-mutant advanced NSCLC patients who received first generation EGFR-TKIs (gefitinib or erlotinib) from December 2009 to November 2014 at Guangdong General Hospital. Of these 515 patients, 65 patients recieved same EGFR-TKI rechallenge, including 51 patients who underwent rebiopsy and secondary EGFR mutation detection after failure of initial EGFR-TKIs. EGFR detection was performed by Sanger sequencing or Amplification Refractory Mutation System (ARMS) methods. Progression-free survival (PFS) and overall survival (OS) were both calculated from commencement of EGFR-TKI rechallenge. Survival data were analyzed using the Kaplan-Meier method and log-rank test.
Results:
EGFR activating mutations still existed in all the 51 patients who received rebiopsy and 18 patients were with T790M mutation while 33 patients were without T790M. The median PFS for the T790M+ and T790M- groups were 1.8 months (95%CI 1.180~2.420) and 2.0 months (95%CI 1.100~2.900), respectively (P=0.261). The median OS for the two groups were 7.7 months (95%CI 6.548~8.852) and 6.8 months (95%CI 4.730~8.870), respectively (P=0.565). No statistical difference was found in PFS or OS between two groups(Figure 1). Figure 1 Fig 1. Kaplan-Meier curves of patients in two groups. (A)Progression-free survival. (B) Overall survival.
Conclusion:
EGFR T790M mutation is neither a predictive nor a prognostic factor for first generation EGFR-TKI rechallenge in EGFR-mutant advanced NSCLC patients, indicating that whether T790M occurs or not, same EGFR-TKI rechallenge could not be recommended as a good strategy to overcome the resistance to first generation EGFR-TKIs.
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MINI 08 - Prognostic/Predictive Biomarkers (ID 106)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:T.E. Stinchcombe, N. Pavlakis
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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MINI08.06 - Prognostic Significance of FGFR1 Amplification in Patients with Lung Squamous Cell Carcinoma (ID 814)
17:20 - 17:25 | Author(s): Y.-. Wu
- Abstract
- Presentation
Background:
The Fibroblast Growth Factor Receptor(FGFR) pathway especially FGFR1 gene copy number gain have attracted continuous attention of researchers for several years. Whereas due to different test methods and distinguishing criteria whether FGFR1 amplification related to patients smoking status or prognosis is still controversial.
Methods:
We used fluorescence in situ hybridization (FISH) to detect the gene copy number in paraffin-embedded tissue sections from 200 cases of pulmonary squamous cell carcinoma patients who underwent surgery in Guangdong Lung Caner Institute(GLCL) from 2008 to 2013. All samples had been identified as primary squamous cell carcinoma by postoperative pathology and informed consent. A tumor is defined as FGFR1 amplification positive when FISH results meet one of the following criteria after reviewing at least 100 tumor cells: (1) FGFR1/CEP-8 ratio≥2; (2) mean number of FGFR1 signals≥6; or if (3) ≥10% tumor cell containing more than 15 FGFR1 signals or large clusters. Among them, sample accord with the 3rd standard was defined as focal amplification.
Results:
Figure 1 We used fluorescence in situ hybridization (FISH) to detect the gene copy number in paraffin-embedded tissue sections from 200 cases of pulmonary squamous cell carcinoma patients who underwent surgery in Guangdong Lung Caner Institute(GLCL) from 2008 to 2013. All samples had been identified as primary squamous cell carcinoma by postoperative pathology and informed consent. A tumor is defined as FGFR1 amplification positive when FISH results meet one of the following criteria after reviewing at least 100 tumor cells: (1) FGFR1/CEP-8 ratio≥2; (2) mean number of FGFR1 signals≥6; or if (3) ≥10% tumor cell containing more than 15 FGFR1 signals or large clusters. Among them, sample accord with the 3rd standard was defined as focal amplification.
Conclusion:
Our results suggested that FGFR1 focal amplification might be an independent risk factor for patients overall survival. Patients with FGFR1 amplification were more likely to disease recurrence. Clinical characteristic including smoking status were not found in association with FGFR1 amplification, suggesting patients with FGFR1 amplification might not be fully enriched through only clinical factors.
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MINI 26 - Circulating Tumor Markers (ID 148)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:M. Macmanus, C. Aggarwal
- Coordinates: 9/09/2015, 16:45 - 18:15, 205+207
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MINI26.13 - Serial ctDNA Assessment of Response and Resistance to EGFR-TKI for Patients with EGFR-L858R Mutant Lung Cancer from a Prospective Trial (ID 3107)
17:50 - 17:55 | Author(s): Y.-. Wu
- Abstract
- Presentation
Background:
Plasma circulating tumor DNA (ctDNA) has been widely accepted as a form of liquid biopsy to detect EGFR mutations in NSCLC for its high concordance rate with tumor tissues. There are some retrospective studies about the ctDNA quantitative changes of EGFR mutations in EGFR-TKI treatment, but there is no report about serial ctDNA assessment of response and resistance to EGFR-TKI by detecting the dynamic changes of EGFR mutations during the whole course of EGFR-TKI treatment based on prospective clinical trial.
Methods:
Based on a randomized trial initiated to compare erlotinib with gefitinib in advanced NSCLC harboring EGFR exon 21 L858R mutation in tumor tissues (CTONG0901, NCT01024413), we prospectively collected serial plasma samples as preplanned schedule (baseline, one week after treatment, one month after treatment and then every 8 weeks until disease progression) and quantitatively detected EGFR L858R mutation in ctDNA by using fluorescence quantitative polymerase chain reaction. We made a serial ctDNA assessment of response and resistance to EGFR-TKI and its correlation with survival outcomes. Four patients’ serial plasma samples were selected to undergo next generation sequencing (NGS).
Results:
From 108 patients enrolled in the trial, serial plasma of 80 patients were collected as schedule and tested the quantity of L858R. As a whole, the quantity of L858R decreased to the lowest level when patients achieved best response to EGFR-TKI and increased to the highest level when disease progressed. Further analysis by Ward's Hierarchical Clustering Method showed that the dynamic changes of quantity of L858R could be categorized into two groups, Ascend Group and Stable Group (Figure 1A). Median progression-free survival (PFS) was 11.1 months (95%CI=6.6-15.6) and 7.5 months (95%CI=1.4-13.6) in two groups, respectively (HR=0.57, 95%CI=0.34-0.97, P=0.035) (Figure 1B). Median overall survival was 20.1 months (95%CI=15.7~24.5) vs. 16.4 months (95%CI=13.3~19.6) (HR=0.73, 95% CI =0.38~1.38, P=0.322). In multivariate Cox proportional hazards regression analysis, changing group was independent predictive factor for PFS. In plasma samples of 4 patients underwent NGS, similar dynamic changing characteristics were confirmed and more genetic mutations were found. Detailed data will be presented on site.Figure 1
Conclusion:
This is the first report about serial ctDNA assessment of response and resistance to EGFR-TKI by detecting the dynamic changes of EGFR mutation based on a prospective clinical trial. The quantity of plasma L858R has different changing patterns during EGFR-TKI treatment and higher L858R mutation abundance on EGFR-TKI resistance is correlated with longer PFS.
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