c-Met is overexpressed and has prognostic significance in a variety of solid tumors, including breast cancer (17%), lung cancer (40%), gastric cancer (>95%), colorectal cancer (78%), ovarian cancer (31%), head and neck cancer (>58%), kidney cancer (70%), and pancreatic cancer (>70%).5
Due to the redundant activation of c-Met-directed pathways, many c-Met inhibitors benefit only small subsets of patients with tumors driven by signaling through c-Met.6,7
- Necessitates selection of patients with c-Met amplification
c-Met protein overexpression is seen in a majority of NSCLCs.8
- 50% of primary EGFR-TKI-naive NSCLC tumors showed high c-Met expression while only 3% showed c-Met amplification.7
Very high levels of c-Met overexpression have been found in NSCLC tumor samples harboring an EGFR mutation.7
- A significant correlation was found between c-Met expression and EGFR mutations (P = .029).
In advanced-stage NSCLC, c-Met mutations have a deleterious effect on overall survival (hazard ratio 23.65; P = .005) and indicate poor prognosis.9