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In Ae Kim
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-030 - Cumulative Smoking Dose Affects the Clinical Outcomes of EGFR-Mutated Lung Adenocarcinoma Patients Treated with EGFR-TKIs (ID 9159)
09:30 - 16:00 | Presenting Author(s): In Ae Kim
- Abstract
Background:
EGFR-mutated lung cancer patients are mostly found in never smoker but at least one third of the patients are ever smokers. Clinical outcomes are known to be variable according to the smoking history among EGFR-mutated lung adenocarcinoma patients when treated with EGFR-TKIs. The aim of this study is to investigate whether cumulative smoking dose affects the clinical outcomes such as progression-free survival (PFS) and overall survival (OS) in EGFR-mutated lung adenocarcinoma patients treated with EGFR-TKIs
Method:
We retrospectively analyzed 142 advanced or recurrent lung adenocarcinoma patients who harbored activating EGFR mutations (exon19 deletion or exon 21 L858R) and had received gefitinib, erlotinib or afatinib. Detailed smoking histories and smoking dose were obtained from all patients. The patients were classified into 4 groups by cumulative smoking dose (never smoker, ≤10 pack-years (PYs), 11-30 PYs and > 30 PYs). PFS and OS were analyzed according to smoking subgroups by Kaplan- Meier curves.
Result:
Among 142 EGFR-mutated patients, 91(64.1%) were never-smokers, 12(8.5%) were minimal smokers with ≤10 PYs, 22(15.5%) were moderate smokers with 11-30 PYs, and 17(12%) were heavy smokers with more than 30 PYs. Cumulative smoking dose was inversely associated with median PFS in dose-dependent manner with statistical significance. (11.8 months, 10.9months, 7.4 months, 3.9 months. p < 0.05). Kaplan-Meier curves of OS showed statistically significant negative association between cumulative smoking dose and median OS. (33.6months, 26.3months, 20 months, 8.9months: p<0.001) However, minimal smoker group less than 10 PYs showed very similar clinical outcomes of PFS and OS with never smoker group. In the multivariate analysis adjusted for age, sex, performance status, stage, and time point of EGFR-TKI treatment, cumulative smoking dose was an independent predictive factor for the disease progression (hazard ratio, 3.29; 95% confidence interval(CI), 1.68-6.45 p <0.001) and short OS(HR 4.3, 95% CI 2.1-8.7 p<0.001) to EGFR-TKIs.
Conclusion:
Cumulative smoking dose inversely affects the duration of response and survival to EGFR-TKIs in EGFR-mutated lung adenocarcinoma patients. Profiling of smoking-related gene signatures might be valuable for therapeutic decision besides EGFR mutation test in lung adenocarcinoma patients.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-034 - Liquid Biopsy for EGFR Genotyping Using Cell-Free DNA and Extracellular Vesicular DNA of Pleural Effusion in Pulmonary Adenocarcinoma Patients (ID 9201)
09:30 - 16:00 | Author(s): In Ae Kim
- Abstract
Background:
Pleural effusion is a highly efficient sample for liquid biopsy due to cancer cell enriched components. Liquid biopsy for EGFR genotyping is mostly being done using cell-free DNA. Extracellular vesicles (EVs) are known to carry oncogenic double stranded DNA that is considered as a noble biomarker. We set up to investigate the liquid biopsy using cell-free (cf) DNA and extracellular vesicular (EV) DNA of pleural effusion for EGFR genotyping in pulmonary adenocarcinoma patients.
Method:
Forty nine pleural effusion samples of pulmonary adenocarcinoma patients were evaluated. Non-cellular components after removing cell pellets by centrifuge (400g, 10 min, 4[0]C) were used for liquid biopsy and EVs were isolated by ultracentrifuge method (200,000g, 1 hr, 4[o]C). EV DNA and cf DNA were extracted separately and EGFR genotyping was done by PNA-clamping method. For the analysis of T790M detection, cell block slides were used as rebiopsy sample, when compared with liquid samples.
Result:
Among 31 EGFR-TKI naïve patients with known tissue EGFR genotyping, liquid biopsy using effusion EV DNA showed 100% matching with tissue EGFR genotyping in 19 EGFR mutant cases and detected 3 more EGFR mutant cases in tissue wild type (WT) patients, while liquid biopsy using effusion cf DNA missed 2 cases of tissue-based EGFR mutant patients and found 2 more EGFR mutant cases in tissue WT patients. In 18 patients with acquired resistance to EGFR-TKI, EGFR genotyping using effusion EV DNA detected T790M mutation in 13 of 18 (72.2%) patients, while 11 of 18 (61.1%) patients were detected by using effusion cf DNA, respectively. In contrast, only 3 patients were found to have T790M when using cell block slides.
Conclusion:
Liquid biopsy using pleural effusion is particularly effective for EGFR genotyping than conventional cytology or cell block sample. Liquid biopsy using effusion EV DNA is highly promising for EGFR genotyping, especially detecting T790M mutation, when compared with cf DNA.
