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N. Zhang
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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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P1.01-035 - A Next Generation Sequencing and Characteristics Based Model for Predict Clinical Benefit of Advanced NSCLC Patients (ID 9208)
09:30 - 16:00 | Author(s): N. Zhang
- Abstract
Background:
The development of targeted therapies has revolutionized the treatment of non-small cell lung cancer. Interrogating the status of driver mutations has become routine practice. In this study, we applied next-generation sequencing to investigate the association between molecular signature and clinical benefit.
Method:
We performed capture-based targeted ultra-deep sequencing on 204 samples obtained from NSCLC patients at a single center, including 93 FFPE, 70 fresh tissue and 41 plasma samples. One hundred and twenty two samples were subjected to a panel consisting of 8 driver genes; 50 samples were subjected to a 56-gene panel. The remaining 32 samples were subject to a 168 gene panel.
Result:
In 159 TKI-naïve patients, driver mutation was identified in 95.2% of (79/83) patients using the 8-gene panel; among them, 65.1% (54/83) carried EGFR mutations. Larger panels identified mutations in 68.1% of patients; 21% carried mutations other than driver mutations. Treatment-naïve patients were primarily subject to the 8-gene panel; in contrast, patients progressed on chemotherapy were subject to larger panels. Seventy-two percent of patients (80/111) undergone matched targeted therapy (MTT) according to sequencing results had a significantly longer PFS than 29 patients who chose chemotherapies despite the fact of harboring driver (p=4.58x10[-4] HR=0.342, 95% CI: 0.158, 0.74). Next, we investigated whether the number of EGFR mutations a patient carries and the presence of concurrence EGFR amplification have an effect on PFS. Our data revealed that both parameters are not associated with PFS. Among 46 patients receiving chemotherapy, patients with KRAS mutations were associated with a shorter PFS, 133 days vs 207 days (p= 0.073, HR=2.06 95% CI; 0.791, 5.36). For TKI-naïve patients, primary tumor tissue was collected from 86 patients and tumor tissue from metastatic lymph nodes was collected from 35 patients. Interestingly, we observed that lymph node samples had a higher maximum mutation allelic fraction (MAF) than primary lung tumor samples in patients with distance metastasis, especially with visceral metastasis (p=0.0986); such trend was not observed in patients without distant metastasis. We also analyzed samples obtained after TKI-treatment. Among 36 TKI-treated patients, patients with visceral metastasis were more likely to harbor TP53 mutations (p=0.04), which were primarily missense mutations not loss of function mutations, primarily seen in tumorigenesis. TP53 missense mutations can potentially promote distant visceral metastasis after the development of resistance to TKIs.
Conclusion:
Our study highlighted the utility of sequencing-based screening technologies and characteristics in providing treatment guidance.
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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): N. Zhang
- 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.
