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Jie Lin
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MA21 - Non EGFR/MET Targeted Therapies (ID 153)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:Benjamin Besse, Michael Thomas
- Coordinates: 9/10/2019, 14:30 - 16:00, Vienna (2016)
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MA21.02 - Genomic Origin and EGFR-TKI Efficacy of Pulmonary Adenosquamous Carcinoma (Now Available) (ID 578)
14:30 - 16:00 | Author(s): Jie Lin
- Abstract
- Presentation
Background
Lung adenosquamous carcinoma (ASC) is a heterogeneous disease that comprises of both adenocarcinoma (AC) and squamous cell carcinoma (SCC) components. Their genomic profile, evolutionary origin, and clinical management remain controversial. Objective of this study is to define the genomic origin of this heterogeneous tumor by independent genomic analyses of the AC and SCC components.
Method
Surgical ASCs were collected. AC component and SCC component were obtained separately by microdissection, and Lymph node (LN) metastases were gathered. Targeted sequence was performed for the two components using a 1021-gene panel, independently. Evolutionary relationship of the two components was analyzed. The independent cohorts of adenocarcinoma (n=170) and squamous cell carcinomas (n=62) were used for comparison. EGFR and concomitant mutations with response to EGFR-TKI were analyzed. Retrospective 517 ASCs underwent EGFR detections were collected from 11 centers. Objective response rate (ORR), disease control rate (DCR) and progression free survival (PFS) were analyzed in EGFR-positive patients received EGFR-TKIs.
Result
28 ASCs were collected. NGS was performed on AC component and SCC component samples, respectively. The most frequent alterations in 28 ASCs were EGFR mutation (79%), TP53 mutation (68%), MAP3K1 mutation (14%), EGFR amplification (32%), and MDM2 amplification (18%). 27 patients had trunk variations in the both components suggesting the monoclonal origin of ASCs. The prevalence of trunk mutations was correlated to those of AC, indicating that ASC might originate from AC. Only one patient did not carry any trunk variations between AC and SCC components, which were clearly and geographically distinguishable under the microscope. 22 had AC component or/and SCC component specific variations suggesting the common event of branch evolution. The 23 LNs of 13 patients mainly contained AC and ASC components (AC, SCC, and ASC: 11, 1, and 11, respectively), and each of the LNs carried the trunk mutations of the primary ASC. Like pure AC, the alterations of L858R and Exon 19 Dels of EGFR were common in the 28 ASCs. Unfortunately, these patients have not been treated with TKIs. Further, of 517 retrospective ASCs from 11 centers, 51.8% were EGFR-positive. For the 129 EGFR-positive ASCs who had received TKIs, the ORR and DCR were 56.6% and 89.1%, respectively. The median PFS was 10.1 months (95% CI: 9.0-11.2).
Conclusion
The AC and SCC components share a monoclonal origin, and a majority have branching evolution. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR-TKIs.
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-26 - Epithelial Growth Factor Receptor Mutation Pattern in Non-Small Cell Lung Cancer of Xuanwei Region in Southwestern China (Now Available) (ID 131)
09:45 - 18:00 | Presenting Author(s): Jie Lin
- Abstract
Background
The incidence and mortality rate of lung cancer in Xuanwei region are among the highest in China. A previous study reported that non-smoking female lung cancer patients in Xuanwei exhibit different EGFR mutation patterns compared with the patterns seen elsewhere in Asia. A unique environment, ethnic group and certain susceptible population may have certain genetic background. Investigating EGFR mutation distribution of NSCLC patients in Yunnan province especially in Xuanwei region is meaningful.
Method
A meta-analysis was conducted to identify the distinctive pattern of EGFR mutations in NSCLC patients in Xuanwei. Electronic databases were comprehensively searched and relevant literature with data were retrieved. The odds ratios (OR) for each EGFR mutation between Xuanwei and other regions were calculated, and the absolute incidence of EGFR mutations in Xuanwei was pooled. Subgroup analyses were performed for different EGFR mutation subtypes.
Result
Five relevant studies with a total of 1,058 NSCLC patients from Yunnan province in southwestern China were conducted. 337 were from Xuanwei and 721 were from other regions; The overall EGFR mutation rate across studies ranged from 34.90% to 55.56%（Table 1）. The results revealed a higher incidence of uncommon EGFR mutations (p<0.001), but a lower incidence of common EGFR mutations (p<0.001) in Xuanwei region compared with other regions. The pooled incidence of uncommon and common EGFR mutations in Xuanwei were 62.7% and 37.3%, respectively (Table 2). More specifically, compared with other areas, patients from Xuanwei harbored a higher frequency of exon 20 S768I (P<0.001) and exon 18 G719X + 20 S768I mutations (P<0.05), but had a lower frequency of 19 deletion (p<0.001)(Table 3).
Conclusion
To summarize, Xuanwei patients carrying EGFR mutations exhibit distinct EGFR mutation spectrum compared with other regions, with higher uncommon mutations but lower common mutations. The Xuanwei pattern provides an important model to study the etiology or risk factor for EGFR uncommon mutations.
