Abstract 242P
Background
The role of tumor microenvironment (TME) features in advanced (a) oncogene addicted Non-Small Cell Lung Cancer (NSCLC) is unclear. We assessed their distribution and prognostic value in EGFR mutant (+) aNSCLC and controls.
Methods
This is a three-centers, retrospective study of patients (pts) treated in 2008-2023 for EGFR exon 19 deletion/L858R+ or ALK/ROS+ or EGFR/ALK/ROS1 negative (-). Using digitalized hematoxylin-eosin baseline slides (magnified at 20x), a pathologist analyzed TME. Tumor-infiltrating lymphocytes (TILs) were + at >10% presence in stromal tissue; fibrosis, tertiary lymphoid structures (TLSs), lymphangitis, necrosis were + at 1%. Overall survival (OS) from first line was compared in feature + vs - in each cohort. Multivariable model included age, gender, PS ECOG (PS), number of metastatic sites (N sites), brain metastases, TME features.
Results
The study included 332 pts: 220 EGFR+, 54 ALK/ROS1+, 58 EGFR/ALK/ROS1-. Fibrosis was prevalent in EGFR+ (p=0.03); necrosis, lymphangitis in EGFR/ALK/ROS1- (p=0.02 and 0.004). In EGFR+, 206 pts were analyzed for OS: 67 had first line osimertinib, 115 gefitinib/erlotinib, and 24 chemotherapy (CT). Median age was 66 (IQR 58-74), 145 (70%) were female, 127 (62%) had no smoking habit. In necrosis+, mOS was 20.8 (95%CI 16.4 - 26.2) vs 35.5 (95%CI 28.2 - 44.2) months in - (p<0.0001). Necrosis (p<0.0001), PS≥2 (p=0.001), N sites≥2 (p=0.003) were independently associated with shorter OS. In ALK/ROS1+, 31 pts had first line target therapy, 19 had CT. mOS was 22.1 (95%CI 10.1 - 40) in fibrosis+ vs 105 (95%CI 67 – NR) months in - (p=0.001). Fibrosis, PS≥2 were independently associated with shorter OS (p=0.02 each). In EGFR/ALK/ROS1-, 43 pts had first line CT-immunotherapy, 13 had CT, with no significant association feature-OS. Table: 242P
| EGFRN=220N(%) | ALK/ROS1N=54N(%) | EGFR/ALK/ROS1-N=58N(%) | p* | |
| Fibrosis | 0.03 | |||
| + | 154 (70) | 32 (59) | 29 (50) | |
| - | 50 (24) | 18 (34) | 20 (34) | |
| NE | 16 (6) | 4 (7) | 9 (16) | |
| Necrosis | 0.02 | |||
| + | 60 (27) | 19 (35) | 28 (48) | |
| - | 141(64) | 34 (63) | 29 (50) | |
| NE | 19 (9) | 1 (2) | 1 (2) | |
| Tils | 0.1 | |||
| + | 73 (33) | 10 (18) | 19 (33) | |
| - | 130 (59) | 38 (70) | 36 (62) | |
| NE | 17 (8) | 6 (12) | 3 (7) | |
| TLSs | 0.5 | |||
| + | 37 (17) | 6 (11) | 11 (19) | |
| - | 160 (73) | 42 (78) | 40 (69) | |
| NE | 23 (10) | 6 (11) | 7 (12) | |
| Lymphangitis | 0.004 | |||
| + | 94 (43) | 31 (57) | 34 (59) | |
| - | 108 (49) | 19 (35) | 14 (24) | |
| NE | 18 (8) | 4 (8) | 10 (17) |
Conclusions
TME features vary in distribution and prognostic role across aNSCLC drivers, warranting further investigation into differential signaling pathways.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, Pfizer , MSD, Boehringer-Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, Takeda, Sanofi; Financial Interests, Personal, Expert Testimony: Ose Immunotherapeutics; Financial Interests, Institutional, Invited Speaker: Merck Portugal; Non-Financial Interests, Personal, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Personal, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Personal, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. 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, Advisory Board: Amgen, AstraZeneca, Beigene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi aventis, Springer Healthcare Ltd, 4D Pharma; Financial Interests, Institutional, Expert Testimony: AbbVie, Da voltera, Eli Lilly, Ellipse pharma Ltd, F-Star, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Socar research, Taiho oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD, AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi Sankyo, GSK, Janssen, Ose immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Turning Point Therapeutics, Genmab, Taiho, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Funding: Cristal 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: Sandoz, Viatris; Financial Interests, Personal, Funding: AstraZeneca, Amgen. All other authors have declared no conflicts of interest.