Exon 5 Mutation Indicates Poor Progression-Free Survival for Patients with Stage IV NSCLC.

Background: Genetic mutations are quite common in non-small cell lung cancer (NSCLC), however, their prognostic value remains controversial.

Methods: This study explored the mutational landscape of tumor samples from patients with advanced NSCLC by next-generation sequencing (NGS). A total of 101 NSCLC patients in stage III or IV receiving first-line treatment were included.

Results: mutation was the most frequent genetic alteration in NSCLC tumors (68%), followed by (49%), (12%), (9%), and (9%) mutations. Among 85 patients with stage IV NSCLC, first-line targeted therapy remarkably prolonged progression-free survival (PFS) of patients compared with first-line chemotherapy ( = 0.0028). Among 65 patients with stage IV NSCLC whose tumors harbored , , , or mutations, first-line targeted therapy substantially prolonged the PFS of patients ( = 0.0027). In patients with mutations who received first-line targeted therapy or chemotherapy, missense mutation was the most common mutation type (36/78), and exon 5 represented the most common mutated site (16/78).

Conclusions: mutation in exon 5 could independently predict poor PFS of patients with stage IV NSCLC after the first- line treatment. Moreover, mutations in exon 5 and were associated with shorter PFS of such patients whether after first-line chemotherapy or targeted therapy, respectively. Thus, these patients should be given immunotherapy or immunochemotherapy.