Abstract 2503: The role of APOBEC in early stage-EGFR mutant non-small cell lung cancer

Abstract Background: The APOBEC family of zinc-coordinating enzymes converts cytosines to uracils in single-strand DNA. APOBEC plays a crucial role in the mutation process of non-small cell lung cancer (NSCLC) and is essential for both adaptive and innate immune responses. This study aims to evaluate the role of the APOBEC mutation signature in early-stage non-small cell lung cancer (NSCLC). Methods: We conducted whole-exome sequencing and whole-transcriptome sequencing using fresh tissue or formalin-fixed paraffin-embedded samples from 100 patients diagnosed with pathologic stage II-IIIA non-squamous NSCLC, all of whom underwent complete resection between January 2014 and December 2020 at Samsung Medical Center. This study aimed to assess the impact of APOBEC enrichment on disease-free survival (DFS), progression-free survival (PFS) of EGFR-TKI, and overall survival following recurrence. Results: Median follow-up duration was 58. 2 months (range, 11. 3-141. 1). Of the patients, 74% were never-smokers, and 52% had stage III disease. Among the 100 patients, 18 (18%) exhibited APOBEC enrichment (≥ 2). The median RFS was 25. 2 months (95% CI, 17. 3-33. 2). Notably, APOBEC enrichment did not show a significant association with DFS (P=0. 14). Among the 76 patients who experienced radiological recurrence, 69 received EGFR-TKI as first-line treatment. The median PFS for EGFR-TKI was 22. 9 months (95% CI, 13. 0-32. 8). However, within this group, patients with APOBEC enrichment showed a shorter PFS compared to those without APOBEC enrichment (8. 1 months vs. 24. 6 months, P=0. 014). In multivariate analysis, poor PFS of EGFR-TKI was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR=1. 9, P=0. 04), TP53 mutation (mutation vs. wild type, HR=2. 1, P=0. 03), and APOBEC enrichment (≥ 2 vs. 2, HR=2. 2, P=0. 02). Overall survival from the starting EGFR-TKI was 61. 1 months and 21. 7 months for patients with APOBEC enrichment or patients without APOBEC enrichment, respectively (P=0. 027). Conclusions: APOBEC mutation signature may be presented at initial diagnosis of early-stage EGFR mutant NSCLC and it was associated with poor PFS of EGFR-TKI and overall survival. Citation Format: Hyun Ae Jung, Jinyeong Lim, Yoon-La Choi, Sehhoon Park, Jong-Mu Sun, Myung-Ju Ahn, Se-Hoon Lee. The role of APOBEC in early stage-EGFR mutant non-small cell lung cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2503.