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D. Zheng
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-037 - Circulating Tumor DNA Clearance During Treatment Associates with Improved Progression-Free Survival (ID 9653)
09:30 - 16:00 | Author(s): D. Zheng
- Abstract
Background:
Therapeutic selection has been shown to lead to marked clonal evolution, thus revealing limitations in imaging scan as a monitoring method, which does not reflect biological processes at a molecular level. However, currently, response assessment of patients with non-small cell lung cancer (NSCLC) primarily relies on imaging scans, necessitating the development of methodologies for dynamic monitoring of treatment response. We evaluated ctDNA as a tumor clonal response biomarker.
Method:
We screened 831 advanced NSCLC patients with a mixture of prior treatment exposure by performing capture-based ultra-deep targeted sequencing on plasma samples using a panel consisting of 168 NSCLC-related genes. Eighty-six patients with driver mutations and a minimum of 2 evaluation points in addition to baseline were included for further analysis.
Result:
At baseline, 79.9% patients harbored at least one mutation from this panel; the remaining 20.1% had no mutation detected. Sixty-nine percent of patients (570/831) harbored driver mutation. Patients harboring 2 mutations or fewer at baseline had a median progression-free survival (PFS) of 7.4 months; in contrast, patients harboring more than 2 mutations had a median PFS of 3.8 months (P=6.6x10[-5 ]HR=0.34), suggesting a significant inverse correlation between number of mutations at baseline and PFS. Next, we evaluated the ability of ctDNA as a tumor clonal response biomarker in 86 patients with a minimum of 2 follow-ups. After a median follow-up of 314 days, 64 patients (74.4%) reached disease progression. During treatment, 46 patients, treated with either matched targeted therapy (MTT) or chemotherapy, had a minimum of one time of ctDNA clearance, occurring from 1.6 months to 7.5 months after the commencement of treatment, with a median PFS of 8.07 months, an overall response rate (ORR) of 41% and a disease control rate (DCR) of 93%. Median overall survival (OS) for this group has not reached. In contrast, 40 patients who had consistent detectable ctDNA throughout the course of treatment had a median PFS of 3.47months, a median OS of 425 days, an ORR of 20% and a DCR of 53%. Our data revealed that patients with a minimum of one time ctDNA clearance are associated with a better ORR (p=0.05), DCR (p=5.9x10[-5]), a longer PFS (p=5.4x10[-10 ]HR=0.21) and OS (p=2.3x10[-5 ]HR=0.21), regardless the type of treatment commenced and the time of evaluation.
Conclusion:
This real world study comprising a heterogeneous population reveals the predictive and prognostic value of ctDNA and warrants further investigations to explore its clearance as a surrogate endpoint of efficacy.
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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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P3.01-052 - The Prevalence and Genotype Distribution of Dual in Cis EGFR Mutations in Chinese Advanced Non-Small Cell Lung Cancer Patients (ID 9721)
09:30 - 16:00 | Author(s): D. Zheng
- Abstract
Background:
The prevalence of EGFR mutation has been well elucidated in different ethnicities. Recently, increasing attention has been given to dual EGFR mutations. However, less attention has been invested in dual in cis EGFR mutations. Until now, none of retrospective or prospective research has focused on dual in cis EGFR mutations except case reports.
Method:
In this real world study, we performed capture-based ultra-deep targeted sequencing on circulating tumor DNA to identify and investigate the prevalence and genotype distribution of dual in cis EGFR mutations in 3,000 Chinese advanced NSCLC patients. This cohort consisted of both treatment-naïve and previously treated patients. Ten milliliter of peripheral blood was collected from every patient and a minimum of 50ng of ctDNA was needed for library construction. The panel covered critical exons and introns of 168 genes (160kb of human genomic regions).
Result:
1,266 patients harbored EGFR mutant in this cohort; among them, 501 patients harbored 19 deletions, 489 harbored L858R, and the remaining harbored other EGFR mutations. We identified 1.5% patients (19/1,266) harboring dual in cis EGFR mutations. Among them 37% (7/19）carried two rare EGFR mutations and the remaining 63% (12/19) carried EGFR L858R in combination with a rare mutation. No patient carried EGFR 19 del in combination with other rare mutations was identified in this cohort, suggesting EGFR 19del is a stronger oncogenic driver than EGFR L858R (p=0.000197, Fisher’s exact test). For patients carried two rare mutations, both mutations were either located on exon 18 or exon 21. The allelic fractions (AF) of both mutations were similar. The AF of either EGFR mutations was the maximum AF in all patients, demonstrating the clones harboring EGFR mutations were major clones. Interestingly, 1 patient carried additional KRAS mutation and 2 patients had EGFR amplification.
Conclusion:
In cis dual EGFR mutation was rare (1.5%) in EGFR mutant Chinese advanced NSCLC patients. EGFR L858R was significantly more likely to couple with a rare in cis dual mutation than 19 del. EGFR 19del might be a stronger oncogenic driver than EGFR L858R.
