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Cocktail & Poster Display session

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

Date

04 Oct 2023

Session

Cocktail & Poster Display session

Presenters

Lodovica Zullo

Citation

Annals of Oncology (2023) 8 (suppl_1_S5): 1-55. 10.1016/esmoop/esmoop101646

Authors

L. Zullo1, M.R. Ghigna2, W.S. Zrafi3, A. Marinello1, D. Vasseur4, M. Frelaut1, P. Abdayem1, M. Tagliamento1, P. Lavaud1, A. Gazzah5, L. Friboulet6, J. Scoazec2, J. Remon1, F. Barlesi1, B. Besse1, D. Planchard1, M. Aldea1

Author affiliations

  • 1 Department Of Cancer Medicine, Institut Gustave Roussy, 94805 - Villejuif, Cedex/FR
  • 2 Department Of Pathology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 3 Radiation Epidemiology Team, Center For Research In Epidemiology And Population Health, Inserm U1018, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 4 Department Of Medical Biology And Pathology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 5 Drug Development Department, Institut Gustave Roussy, 94805 - Villejuif, Cedex/FR
  • 6 Inserm U981, Institut Gustave Roussy, 94805 - Villejuif/FR

Resources

This content is available to ESMO members and event participants.

Abstract 80P

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 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: 80P

Survival 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) 0.03
TILs (44/120) 27.6 (26.5 - NR) vs 35.5 (27.8 - 44.7) 0.9
TLSs (21/116) 38.1 (26.6 - NR) vs 33.5 (27.4 - 44.7) 0.9
Necrosis (35/118) 23.7 (21.4 - 39.3) vs 36.8 (30.8 - 51.3) 0.01
Lymphangitis (49/118) 27.7 (23.3 - 41.5) vs 36.8 (27.8 - 51.3) 0.1
Antiangiogenics, n=30 (1 pt received antiangiogenic + anti PD-1)
Fibrosis (20/25) 39.3 (35.8 - 87.4) vs 21.1 (19.8 - NR) 0.016
Necrosis (6/24) 30.2 (16.1 - NR) vs 44 (33.5 - 87.4) 0.19
Multivariable model
HR (95%CI) p
Necrosis 1.76 (1.02 - 3.05) 0.04
Fibrosis 0.46 (0.23 - 0.89) 0.02
PS 2.09 (1.11 - 3.97) 0.02
N sites 1.35 (1.06 - 1.70) 0.01
.

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.

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