182P - METHRO: Multicentric study of risk of thrombosis in patients with NSCLC harboring a METexon 14 skipping mutation

Background

Thrombotic Events (TEs) manifest in 5-14% of whole population with non-small cell lung cancer (NSCLC), with a significant impact on patient morbidity and mortality. The prevalence of TE in patients with a METexon14 skipping (METex14) NSCLC needs to be further explored.

Methods

We conducted an international retrospective study (Gustave Roussy and Dana Farber Cancer Institute) to investigate the TEs risk among patients with advanced NSCLC harboring METex14 between August/2009 and November/2023. TEs were defined as deep vein thrombosis (DVT), pulmonary embolism (PE), or arterial events occurring during cancer evolution or within the 6 months before cancer diagnosis. Our primary objective was to evaluate the cumulative incidence of TE in this population.

Results

Eighty-four patients were included in the final analysis. Median age was 72 years, 52% patients were women, 68% adenocarcinoma, squamous (12%) other (20%), 46% of patients were never-smokers. Out of all patients, 51% patients were treated with MET-inhibitors (51% in the first-line setting). METex14 co-existed with other oncogene-drivers in 2 pt presenting ALK-fusion, 2 pt with common EGFR-mutation and 1pt with KRAS (Q61H) mutation. After a median follow up of 29 months, 40 out of 84 patients (48%) experienced at least 1 TE: 23 (27%) had PE, 18 (21%) had DVT, 2 (2.4%) had ischemic stroke. There were no significant clinical differences between pt with TE vs no-TE. The median time to onset the first TE was 12.3 month. Cumulative incidence of TE at diagnosis of advanced disease, 6, 12, 24 and 36 months after diagnosis was 6%, 26%, 31%, 40%, 47%, respectively. All patients with METex14 and co-existing genomic alterations had at least a TE event. In the multivariable analysis TEs were not statistically associated with histology subtype (non-squamous/ squamous, p=0.74), gender (p=0.88), age (< 65 years / > 65 years, p=0.58) and smoking (p=0.62).

Conclusions

Almost half of patients with a diagnosis of advanced METex14-mutant NSCLC may experience a TEs. The TEs risk was not associated with specific clinical characteristics.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Aldea: Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Funding: AstraZeneca, Sandoz; Non-Financial Interests, Personal, Member, Member of the Education Committee: IASLC. P. Lavaud: Financial Interests, Personal, Other: Janssen, AstraZeneca, Sanofi, Amgen, Astellas, Ipsen; Financial Interests, Personal, Research Grant: Servier. M. Frelaut: Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Ipsen; Non-Financial Interests, Personal, Advisory Role: SOFOG, EORTC, INCA; Non-Financial Interests, Personal, Member: EORTC, ASCO, SOFOG. D. Planchard: Financial Interests, Personal, Invited Speaker: AstraZeneca, AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Samsung. 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. M. Awad: Financial Interests, Personal, Invited Speaker: Genentech, Bristol Myers Squibb, Merck, Lilly, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, Gritstone, ArcherDX, Mirati, NextCure, Novartis, EMD Serono, Panvaxal/NovaRx; Financial Interests, Personal, Research Grant: AstraZeneca. 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. J. Remon Masip: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Janssen, Merck, Takeda; Financial Interests, Personal, Other, Travel, Accommodation: Ose Immunotherapeutics; Financial Interests, Institutional, Advisory Board: Edi Mack; 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. All other authors have declared no conflicts of interest.