Consistency of c‐Met protein overexpression over time in patients with non‐squamous non‐small cell lung cancer

AIMS: The c-Met signalling pathway is dysregulated in non-small cell lung cancer (NSCLC), with c-Met protein overexpression emerging as a potentially actionable biomarker given the development of c-Met-targeted antibody-drug conjugates. This retrospective study assessed the consistency of c-Met protein overexpression over time in patients with non-squamous NSCLC and two or more longitudinal biopsy samples (one before treatment, one post-treatment). METHODS AND RESULTS: Samples from 160 patients were analysed for c-Met protein expression. The concordance rate for c-Met protein overexpression between samples was 81.3%, indicating most patients had consistent expression status. Patients with an EGFR mutation had a lower concordance rate (65.8%). Fourteen patients with high discordance (negative to positive) between sampling time points showed a high frequency of oncogenic driver alterations, hence often received targeted therapy before the second sample and had high percentages of cells at 2+ intensity in c-Met immunohistochemistry before treatment. CONCLUSIONS: These results indicate c-Met protein overexpression can be assessed before or after treatment since most patients maintain consistent c-Met status. As targeted therapies may elevate c-Met overexpression over time, retesting may be necessary in those with an oncogenic driver alteration initially diagnosed as c-Met negative.