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

Background

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.

Methods

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.

Results

We included 143 pts: 61 received osimertinib, 58 erlotinib/gefitinib, 24 platinum-based chemotherapy as 1^st 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: 80P

Conclusions

Necrosis and fibrosis impact prognosis in EGFR-mut aNSCLC. Findings in pts treated with antiangiogenics should be further tested on a larger scale.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D. Vasseur: Other, Personal, Other: Roche. P. Abdayem: Financial Interests, Personal, Invited Speaker, lectures: AstraZeneca; Financial Interests, Personal, Other, travel, accommodations, and expenses: Roche, Eli Lilly, Pierre Fabre. M. Tagliamento: Non-Financial Interests, Personal, Member, International Lung Cancer Foundation Fellow: IASLC; Non-Financial Interests, Personal, Member, Lung Cancer Group: EORTC; Other, Personal, Other, Travel and accommodation expenses: Eli Lilly. L. Friboulet: Financial Interests, Personal, Research Grant, grant: Debiopharm, Incyte; Financial Interests, Personal, Research Grant: Relay Therapeutics, Sanofi, Nuvalent; Non-Financial Interests, Personal, Other: Illumina. J. Remon: Financial Interests, Personal, Invited Speaker: Takeda, Merck Sharp & Dohme, Sanofi, Boehringer Ingelheim, Pfizer, OSE Immunotherapeutics, Janssen, Takeda. F. Barlesi: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda, AbbVie, ACEA, Amgen, Eisai, Ignyta; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd., Innate Pharma, Mirati. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Pfizer, Janssen, Onxeo, OSE immunotherapeutics, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genzyme Corporation, Chugai Pharmaceutical, Eisai, Inivata, Ipsen, Turning Point Therapeutics. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, prIME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Personal, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Personal, Principal Investigator: AbbVie, Sanofi, Janssen. M. Aldea: Financial Interests, Personal, Other: Viatris, Sandoz. All other authors have declared no conflicts of interest.