2024 World Conference on Lung Cancer (WCLC) - Posters-P1.12A.03 Outcome and Transcriptomic Features of Dual EGFR and MET Blockade in NSCLC

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This study examines the outcome and transcriptomic features of using dual EGFR and MET blockade in patients with EGFR-mutant non-small cell lung cancer (NSCLC) who developed MET amplification as a resistance mechanism to EGFR inhibitors. The research is based on a retrospective review of data from the Lung Cancer Consortium Singapore collected between 2010 and 2020. <br /><br />MET amplification is identified as a mechanism of resistance in patients undergoing treatment with EGFR inhibitors, with a varying frequency that depends on the prior therapeutic regimen. MET amplification and mutations were detected in 57 patients out of 1945 with metastatic EGFR-mutant NSCLC, with 23 patients receiving MET inhibitors.<br /><br />The study highlights that combined EGFR and MET inhibitor therapy provided a longer progression-free survival (PFS) and a higher response rate compared to MET inhibitor monotherapy. Specifically, dual inhibitor treatment achieved an objective response rate (ORR) of 36.4%, whereas MET inhibitor alone resulted in a 0% ORR. The median PFS was slightly longer for the combination therapy (2.56 months) compared to MET inhibitor monotherapy (2.13 months).<br /><br />The research notes uncertainties regarding the predictive value of MET copy number variations, emphasizing the need for further studies to more accurately determine cut-off values for MET copy numbers. The study also faces limitations due to its retrospective nature, small sample size, and the lack of prospectively collected tissue samples.<br /><br />The study concludes that dual blockade of MET and EGFR has the potential to overcome MET amplification in NSCLC patients, supported by real-world and phase 2 trial results. Ongoing phase 3 trials and future investigations into transcriptomic features are anticipated to optimize treatment strategies.

Asset Subtitle

David Lee

Meta Tag

Speaker David Lee

Topic Metastatic NSCLC – Targeted Therapy

Keywords

EGFR

MET amplification

non-small cell lung cancer

NSCLC

dual blockade

progression-free survival

objective response rate

transcriptomic features

resistance mechanism

retrospective study