Abstract 824: Uncommon EGFR mutations are associated with higher tumor mutation burden (TMB) in non-small cell lung cancer patients

Abstract

Abstract Background: Epidermal growth factor receptor (EGFR) mutation is regarded as a predictor for poor clinical response to immunotherapy in non-small cell lung cancer (NSCLC), for which common EGFR mutations (the L858R point mutation and exon 19 deletions) generally exist lower tumor mutation burden (TMB) level. On the other side, uncommon EGFR mutations exist variable efficacy to tyrosine kinase inhibitors (TKIs) and the treatment for these patients is still controversial. Therefore, we conducted this study to investigate the correlation between uncommon EGFR mutations and TMB. Methods: The tissue samples from a Chinese cohort of 2177 lung adenocarcinoma (LAC) and 500 lung squamous cell carcinoma (LSCC) patients were detected by a 381 genes NGS panel from 3D Medicines, and TMB values were obtained from the NGS sequencing data. We evaluated the correlation between common and uncommon mutations in EGFR and TMB in lung adenocarcinoma and squamous cell carcinoma, respectively. Results: In lung adenocarcinoma, patients with uncommon EGFR mutations (n = 208) had a higher TMB level compared with common EGFR mutations (n = 1027) (medium TMB 6.14 Muts/Mb vs 4.84 Muts/Mb, P = 0.0016), but a lower TMB level than patients without EGFR mutations (n = 942) (medium TMB 6.14 Muts/Mb vs 7.26 Muts/Mb, P = 0.0176). In lung squamous cell carcinoma, the TMB level of uncommon EGFR mutations (n = 21) was significantly higher than common EGFR mutations (n = 20) (medium TMB 12.90 Muts/Mb vs 5.40 Muts/Mb, P < 0.0001). Meanwhile, the medium value of TMB in uncommon mutations group was slightly higher than non-mutations group (n = 459), however, there was no significant difference between the two groups (medium TMB 12.90 Muts/Mb vs 11.29 Muts/Mb, P = 0.2186). Conclusions: Uncommon mutations in EGFR are associated with higher TMB level than common mutations in both lung adenocarcinoma and squamous cell carcinoma. Citation Format: Xudong Shen, Hushan Zhang, Depei Huang. Uncommon EGFR mutations are associated with higher tumor mutation burden (TMB) in non-small cell lung cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 824.