Concordances assessment between MET-positive circulating tumour cells and disease progression in patients with EGFR mutated NSCLC

BackgroundThe use of EGFR-tyrosine kinase inhibitors (TKIs) has shown significant efficacy in treating non-small cell lung cancer (NSCLC) that carries an activating mutation in the epidermal growth factor receptor (EGFR). However, a significant challenge in achieving long-term disease remission in clinical practice arises from the development of acquired resistance, specially, MET dysregulation. Previously, we identified that monitoring MET-positive circulating tumor cells (CTC) could provide the information for predicting disease progression in breast cancer patients. In this study, we investigated the concordance between MET-positive CTCs and disease progression in NSCLC patients.MethodsPatients were prospectively enrolled during their standard treatment course at Samsung Medical Center, Seoul, Republic of Korea. Blood was repetitively collected from the patients during hospital visits. CTCs were isolated using MET-positive CTC isolation kits, an immune magnetophoretic CTC isolation device. Disease progression was evaluated using radiography images based on the modified RECIST, version 1.1. ROC curve analysis was performed to determine the optimal cut-off points for MET-positive CTCs.ResultsTotal 235 EGFR mutated NSCLC patients were analyzed, with 212 (90.2%) of them received EGFR-TKI. During the standard of care, the evaluation of disease progression within two months based on the detection of 8 or more MET-positive CTCs revealed the following metrics for the overall treatment cohort: sensitivity 47.4%, specificity 89.4%, positive predictive value (PPV) 57.8%, negative predictive value (NPV) 84.7%, and accuracy 79.6%. When analyzing the 212 patients who received EGFR-TKI, the results were as follows: sensitivity 50.0%, specificity 89.3%, PPV 55.0%, NPV 87.2%, and accuracy 81.1%.ConclusionsAssessing disease progression within two months using MET-positive CTC detection showed moderate PPV with high specificity in the overall treatment cohort. This performance remained consistent for patients who received EGFR-TKI, suggesting that MET-positive CTC might serve as an indicator for disease progression complementary to current imaging methods in NSCLC patients treated with EGFR-TKI.Legal entity responsible for the studySamsung Medical Center.FundingAbion Inc.DisclosureJ. Park: Financial Interests, Personal, Speaker, Consultant, Advisor: Abion Inc. N.Y. Kim, J. Choi: Financial Interests, Personal, Stocks/Shares: Abion Inc. H. Choi: Financial Interests, Personal, Member: Abion Inc. Y.K. Shin: Financial Interests, Personal, Invited Speaker: Abion Inc.; Financial Interests, Personal, Stocks or ownership: Abion Inc. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Pfizer, Eli Lilly, BMS/Ono, Takeda, Janssen, IMBdx, Merck (German), Novartis, Abion, Abion, BeiGene, ImmuneOncia, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Eli Lilly, Amgen, Yuhan; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, AstraZeneca, Lunit. All other authors have declared no conflicts of interest.