EGFR and non-small cell lung carcinoma: Secondly, although our NMA suggests first-generation EGFR-TKIs combined with chemotherapy are the optimal first-line treatment option for advanced NSCLC patients harboring EGFR 21 Leu858Arg mutation, there is no RCT comparing the second- or third-generation EGFR-TKIs plus chemotherapy with chemotherapy or other treatments, and whether chemotherapy combining the second- or third-generation EGFR-TKIs would be more effective than the first-generation, EGFR-TKI should be further investigated.