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Yuting Yi
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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): Yuting Yi
- 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.
