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The follow-up treatment of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation after drug resistance to EGFR-tyrosine kinase inhibitors (TKIs) have become a hotspot and difficulty at present. Immune checkpoint inhibitors (ICIs) therapy is a new and important choice for these patients, but many studies have shown unsatisfactory efficacy. However, some domestic and foreign studies have shown that ICIs combination therapy is still effective in some patients with positive driver genes and drug resistance after targeted therapy. So, in the era of immunotherapy, what are the differences in the efficacy of different combination immunotherapy strategies for different patients? What are the factors that affect efficacy? What are the interrelationships between these factors and other immunotherapy efficacy prediction biomarkers? All these problems have broad and important research value.