Clinicopathological characteristics and therapeutic outcomes in patients with non-small cell lung cancer harboring mutations.

[OBJECTIVE] To investigate the clinical characteristics and impact of mutations in patients with non-small cell lung cancer (NSCLC).

[METHODS] A total of 2,821 patients with NSCLC who underwent next-generation sequencing were retrospectively included. The frequency and types of mutations and co-mutations were determined, and the clinical outcomes were assessed.

[RESULTS] mutations were identified in 100 samples (3.54%), and 36% were missense mutations. The most frequent co-mutations were (67%) and (31%); 13% of mutations occurred in samples carried and mutations. Notably, 63% mutations did not present druggable driver mutations. mutations were most prevalent in males and smokers. Patients with mutant lung adenocarcinoma (LUAD) and mutations who received EGFR-tyrosine kinase inhibitors (EGFR-TKI) as first-line therapy had a lower objective response rate (ORR, 52.94%). In mutation and wild-type (wt) NSCLC cohort who received first-line chemotherapy, age (hazard ratio [HR], 3.090;  = 0.026) and performance score (HR, 5.848;  = 0.045) were identified as independent predictors of progression-free survival (PFS). Conversely, brain metastasis was an independent predictor of superior overall survival (HR, 0.188;  = 0.011). The patients with wt and mutant Stage IV LUAD who received chemotherapy plus anti-angiogenic therapy significantly improved median PFS compared to chemotherapy alone ( = 0.04).

[CONCLUSIONS] mutations were predominantly males and smokers in NSCLC. mutations conferred a poorer response for -mutant LUAD subgroups who received EGFR-TKIs. Additionally, chemotherapy plus anti-angiogenesis as first-line therapy may be more effective for Stage IV- mutant LUAD with wt.