Multiple mutations in the EGFR gene in lung cancer: a systematic review

BACKGROUND: Lung cancer is a public health problem worldwide. Currently, identifying genetic mutations in the epidermal growth factor receptor (EGFR) has brought significant changes in diagnosing and managing patients with lung cancer. The presence of multiple mutations, defined as the presence of more than one EGFR mutation, has been reported in a few studies. Therefore, we carried out this systematic review to describe the most common multiple mutations in the EGFR gene. METHODS: We conduct a systematic review of descriptive studies, cohorts, and clinical trials published in Scopus, PubMed, Scielo, and Virtual Health Library literature. The inclusion criteria for the systematic review were descriptive studies, cohorts, and clinical trials with the presence of multiple mutations in the EGFR gene. It was followed the Preferred Reporting Items for Systematic Meta-Analyses (PRISMA) guidelines. RESULTS: In the systematic review, 41 articles were included. Four hundred and forty-six cases with multiple mutations in the EGFR gene were found (0.95% of the patients included in the studies). The most prevalent dual mutations observed were T790M + L858R and deletions in exon 19 + T790M. Triple mutations were found in 9 cases (2.017%). According to reports, the presence of T790M mutation in the multiple mutations has been associated with poor clinical outcomes. DISCUSSION: The presence of multiple mutations in the EGFR gene is rare. It is of great importance to consider the T790M mutation since it generates resistance to pharmacological management and has worse outcomes. The most important limitation was that clinical information data and follow-up could not be collected in a large percentage of patients. Therefore, future work should be focused on clinical characteristics, follow-up and repercussions in the treatment of patients with multiple mutations.