80P Tumor microenvironment (TME) defines prognosis of EGFR-mutant non-small cell lung cancer (NSCLC)

Significance of tumor microenvironment (TME) features in EGFR-mutant (mut) Non-Small Cell Lung Cancer (NSCLC) is undefined. We explored their prognostic value in advanced (a) EGFR-mut NSCLC. This is a monocentric, retrospective study of patients (pts) with aNSCLC EGFR exon 19 deletion (del19) /L858R positive (+) treated between 2008-2023. Whole Slide Images (20x magnified) from hematoxylin-eosin baseline slides were analyzed by a pathologist and an oncologist, blinded to clinical data, to describe TME. Tumor-infiltrating lymphocytes (TILs) were considered + in stromal compartment if present in >10% of stromal tissue area. Threshold for + fibrosis, necrosis, tertiary lymphoid structures (TLSs), lymphangitis was 1%. For each TME feature, overall survival (OS), calculated from first-line start, was compared between feature + vs negative (-). Multivariable Cox regression model included age, gender, PS ECOG (PS), number of metastatic sites (N sites), brain metastases (mts), del19/L858R, TME features. We included 143 pts: 61 received osimertinib, 58 erlotinib/gefitinib, 24 platinum-based chemotherapy as 1st line. Among them, 103 (72%) were females, 77 (54%) never smokers, median (m) age was 65.5 (IQR 57 - 73) years, m N sites was 2, PS was >1 in 30 (21%), brain mts were present in 56 (39%) pts, 82 (57%) samples were del19+. Most common biopsy site was lung (66%). Patients had a mOS of 34.9 (95%CI 27.6 - 41.5) months. Factors independently associated with worse OS were necrosis, PS >1, N sites >2. Fibrosis was independently associated with longer OS. In a subgroup of pts treated with antiangiogenics in any line (n=30), no OS difference was seen in baseline necrosis+ vs –Table: 80PSurvival analysis n=143+/evaluable samples+/- mOS (95%CI)p (log-rank)Fibrosis (92/122)38.1 (27.8 - 51.2) vs 23.7 (21.5 - 35.1)0.03TILs (44/120)27.6 (26.5 - NR) vs 35.5 (27.8 - 44.7)0.9TLSs (21/116)38.1 (26.6 - NR) vs 33.5 (27.4 - 44.7)0.9Necrosis (35/118)23.7 (21.4 - 39.3) vs 36.8 (30.8 - 51.3)0.01Lymphangitis (49/118)27.7 (23.3 - 41.5) vs 36.8 (27.8 - 51.3)0.1Antiangiogenics, n=30 (1 pt received antiangiogenic + anti PD-1)Fibrosis (20/25)39.3 (35.8 - 87.4) vs 21.1 (19.8 - NR)0.016Necrosis (6/24)30.2 (16.1 - NR) vs 44 (33.5 - 87.4)0.19Multivariable modelHR (95%CI)pNecrosis1.76 (1.02 - 3.05)0.04Fibrosis0.46 (0.23 - 0.89)0.02PS2.09 (1.11 - 3.97)0.02N sites1.35 (1.06 - 1.70)0.01 Open table in a new tab . Necrosis and fibrosis impact prognosis in EGFR-mut aNSCLC. Findings in pts treated with antiangiogenics should be further tested on a larger scale.