e20757 Background: Activating EGFR mutations are present in up to 15-30% of lung adenocarcinoma patients, and are known genetic drivers that promote tumor cell growth and survival. Recently, EGFR-targeted therapies, including osimertinib +/- chemotherapy, lazertinib and amivantamab, have been shown to significantly improve overall survival. However, augmentation of MET signaling represents a bypass mechanism contributing to resistance to EGFR-targeted therapies. In this single-center retrospective cohort study, we evaluated the effect of MET overexpression at baseline on outcomes in patients with stage IV lung adenocarcinoma treated with first-line osimertinib. Methods: Among patients treated at NYU Perlmutter Cancer Center from 2019 to present, 51 patients with stage IV EGFR-mutant lung adenocarcinoma treated with first-line osimertinib and available tissue samples were selected. Samples were analyzed by immunohistochemistry (IHC) using the VENTANA MET (SP44) RxDx assay. MET expression was classified as high or low using a c-MET H-score ≥200 cutoff. Primary endpoints were progression-free survival (PFS), treatment response at 12 weeks, and overall survival (OS) as defined by RECIST v1.1. Data were analyzed in R by logistic regression and Cox-proportional hazard analysis to assess the association between MET expression and primary endpoints. Statistical significance was set at a threshold of p < 0.05. Results: Cohort characteristics showed that most patients were female (80.4%), never-smokers (68.6%) with median age 64 years (range 38-87) at start of treatment. EGFR Exon 19 deletions were present in 58.8% of patients and Exon 21 L858R mutations in 41.2%. Median PFS was 11 months in the MET-high group and 15 months in the MET-low group (hazard ratio HR 1.07, 95% CI 0.70–1.62; log-rank p = 0.77). Treatment response at 12 weeks did not significantly differ between groups (odds ratio OR 1.03, 95% CI 0.49–2.16). Median OS was 32 months in both groups (HR 1.09, 95% CI 0.63–1.86; log-rank p = 0.76). Conclusions: In this retrospective cohort of EGFR-mutant lung adenocarcinoma patients treated with first-line osimertinib, MET overexpression by IHC was not associated with a statistically significant difference in PFS, treatment response, or OS. However, though not statistically significant, median PFS in the MET-high group was shorter by nearly 4 months compared to the MET-low group. These results are limited by small sample size and retrospective design, but support further evaluation of MET as a potential biomarker and target for upfront EGFR and MET targeting therapies in EGFR-mutant lung adenocarcinoma with concomitant MET alterations. Additionally, future studies with paired tissue for MET expression analysis before and after osimertinib treatment could be performed to assess the dynamic nature of MET expression post-osimertinib.
Lin et al. (Thu,) studied this question.