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Mingming Yuan
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-38 - Identification of FGFR1-3 Fusions in Lung Cancers Using Comprehensive Next-Generation Sequencing (Now Available) (ID 2071)
09:45 - 18:00 | Author(s): Mingming Yuan
- Abstract
Background
Fusions have been described in the fibroblast growth factor receptors (FGFR) 1-3 genes with multiple partners in a variety of tumors. Here we focused on the prevalence of FGFR fusions in lung cancers for whom might benefit from FGFR inhibitors in clinical development.
Method
We reviewed FGFR alterations in 10833 lung cancer patients (pts) who underwent genetic testing at our institute from 2016 to 2019. Mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which covers all exons of FGFR1-3 and specific intron regions containing the break points of fusions. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, MET, ROS1, as well as other oncogenes.
Result
FGFR fusions were identified in 25 lung cancer pts, including 9 adenocarcinoma pts, 4 squamous-cell carcinoma pts, 1 patient with large cell neuroendocrine carcinoma and 11 pts with non-specific pathology. FGFR3-TACC3 fusion was detected in 72% (18/25) of pts and the remaining were previously unreported fusions (table). Concurrent EGFR mutations were identified in 44% (11/25) of pts with FGFR fusions (32%, treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs); 12%, not treated with EGFR-TKIs). PI3K-AKT-MTOR signaling pathway was also activated in 28% (7/25) of pts, and cell-cycle gene alterations were also detected in 16% (4/25) of pts.
ConclusionTable. Frequency of FGFR fusions Fusions
Fusion region
N (%)
FGFR3-TACC3
EX17:EX11
6 (24%)
EX18E:EX11
4 (16%)
EX18E:EX13
2 (8%)
EX17:EX10
2 (8%)
others
4 (16%)
FGFR1-chr8:21672159
EX1:chr8:21672159
1 (4%)
FGFR1-MTUS1
EX19E:EX8
1 (4%)
EFHA2-FGFR1
EX2:EX3
1 (4%)
TNRC18-FGFR1
PMT:EX10
1 (4%)
ZMAT4-FGFR1
EX2:EX2
1 (4%)
ZNF696-FGFR1
EX2:EX18E
1 (4%)
OPALIN-FGFR2
EX6E:EX2
1 (4%)
Total
25 (100%)
FGFR1-3 fusions define a unique molecular subtype of lung cancer. Depending on the concurrent genetic alterations, combined targeted therapy might be an optimal strategy to control tumor growth for these pts.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-54 - Characteristic of MSI-H Lung Cancer Patients Identified with Targeted Next-Generation Sequencing (Now Available) (ID 2435)
10:15 - 18:15 | Author(s): Mingming Yuan
- Abstract
Background
MSI-H/dMMR predicts response to immune oncology (IO) agents and is an approved biomarker for pembrolizumab therapy irrespective of histologic diagnosis. In this study, we retrospectively analyzed a large cohort of lung cancer patients using targeted next generation sequencing to examine the prevalence and clinicopathologic associations of MSI-H in lung cancers.
Method
MSI and TMB status was derived from a 1021 gene targeted next generation sequencing panel. MSI was analyzed using MSIsensor 0.5, that relies on an empirically defined cutoff of MSI score>10%, as MSI-H. TMB analysis interrogated single nucleotide variants, small insertion and deletion, with VAF ≥3 %. TMB-H pts were identified with ≥9 mut/MB (upper quartile of data from geneplus).
Result
5592 lung cancer patients were interrogated in the study, with 4753 lung adenocarcinoma, 559 lung squamous cell carcinoma, 112 small cell lung carcinomas (SCLC), and 168 rare lung cancer types including pulmonary sarcomatoid carcinoma, carcinoid and so on. A total of 12 lung tumors were identified as MSI-H (0.21%), and 5 were lung adenocarcinoma (0.1%), 3 were small cell lung cancer (2.7%), 1 was lung squamous cell carcinoma (0.18%), 2 were pulmonary sarcomatoid carcinomas, and 1 was pulmonary carcinoid (1.8%). The incidence was higher in small cell lung cancer and rare lung cancer subtypes. The average diagnosis age of the 12 patients were 53 years (range: 16-74). All the patients were TMB-H, with the TMB averaged 51.23 mut/Mb (range: 10-70 mut/Mb). Two of the 5 lung adenocarcinoma patients carried EGFR L858R or 19del mutation. One patient who had both NRAS G12V and EGFR Ex20 mutation had tried nivolumab (120mg) for one cycle with deteriorating of cough and progression of disease.
Conclusion
MSI-H is very rare in lung tumors, where it appears to enrich in small cell lung cancer and rare lung cancer subtypes. MSI-H lung cancer patients tend to have a younger diagnosis age. MSI-H may coexist with other driver alterations, including those negatively associated with IO response. Additional investigation is needed to determine efficacy of IO in these patients.
