-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes.

Background: The therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced -mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy.

Material And Methods: We consecutively enrolled stage IV, -mutant, and EGFR-TKI-treated patients with SCC. Patients with wild-type lung SCC and -mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed.

Results: In total, 28 -mutant lung SCC, 41 -mutant lung adenocarcinoma, and 40 wild-type lung SCC patients were included. Among the patients with mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 11.0 months, P<0.001). Comparison of the genomic profiles revealed that -mutant SCC patients had similar mutation characteristics to -mutant adenocarcinoma patients, but differed from those with wild-type SCC. Further exploration of -mutant SCC revealed that mutations in (P = 0.005), (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in (P = 0.025) were associated with improved PFS.

Conclusions: -mutant lung SCC has a worse prognosis than -mutant adenocarcinoma. Mutations in other genes, such as , , , or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with -mutant SCCs receiving EGFR-TKIs.