EGFR assessment using next generation sequencing as a reflex testing on surgically resected non-squamous non-small cell lung carcinoma.

8539 Background: EGFR status assessment is mandatory in early stage (IB-IIIA) non-squamous non-small cell lung carcinoma (NS-NSCLC), but whether NGS methods should be used as reflex testing for this evaluation in daily practice is controversial. However, co-occuring mutations, notably TP53 mutations, may have an impact on tumor behavior and prognosis, and so, on future adjuvant therapeutic strategies. Methods: EGFR mutations were assessed prospectively using NGS (Oncomine Precision Assay genes panel) in 720 NS-NSCLC surgically resected between January 2021 and September 2022 in a single institution (LPCE, Nice, France). PD-L1 expression was evaluated in all tumors. Disease free survival (DFS) analysis was available in 675/720 (94%) patients. Results: EGFR mutations were detected in 83/720 (11.5%) cases. A common non-compound EGFR mutation (L858R or del19) was observed in 62/83 (75%) cases. 12/83 (14%) and 9/83 (11%) tumors had a rare non-compound and compound EGFR mutations, respectively. 40/83 (48%) has a co-occuring mutation, including a TP53 (30/40; 75%) mutation, mainly in exon 5, 7 or 8. EGFR/TP53 mutated tumors were significantly associated with higher PD-L1 expression compared to EGFR mutated tumors. A significant correlation was noted between worse DFS and the detection of a mutation in EGFR exon 18 mutation, as well as the detection of a co-mutation in TP53 exon 7 and in MET exon 14. Conclusions: Genomic alteration should be systematically evaluated using an NGS reflex testing in surgically resected NS-NSCLC, since future adjuvant therapeutic decision making may consider the presence of compound EGFR mutations as well as co-occuring mutations in other genes, especially in TP53.