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Life sciences · Journal article
Theoretical and Natural Science · October 13, 2026
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EGFR-TKIs have significantly improved the survival outcomes of patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, substantial heterogeneity in treatment efficacy exists among individuals, and conventional single-gene testing has limitations in guiding therapeutic decision-making. This systematic review focuses on the effects of driver gene co-mutations on the prognosis of targeted therapy in EGFR-mutant NSCLC and explores their value in clinical translation. Literature published from 2022 to 2026 concerning co-mutations and prognosis of targeted therapy in EGFR-mutant NSCLC was systematically retrieved from the PubMed database for summarization and analysis. This review found that TP53 is the most prevalent co-mutated gene in EGFR-mutant NSCLC and is strongly associated with poor prognosis under TKI monotherapy. Phase III clinical trials have confirmed that TKI combined with chemotherapy significantly prolongs median progression-free survival compared with TKI monotherapy among patients with EGFR mutations accompanied by tumor suppressor gene co-mutations. NGS multi-gene panels serve as the technical foundation for comprehensive co-mutation assessment. In summary, driver gene co-mutations play a critical role in prognostic stratification for EGFR-mutant NSCLC treatment. Taking co-mutation status into account helps identify high-risk patients who may benefit from intensified treatment, supporting more precise and individualized targeted therapy.