The Use of Cytotoxic Drugs as First Line Chemotherapy for EGFR (+) Nonsquamous NSCLC: A Network Meta-Analysis

OBJECTIVE: To assess the use of cytotoxic drugs as first-line chemotherapy for nonsquamous non-small-cell lung cancer (NSCLC) with EGFR mutation. METHOD: This study uses the network meta-analysis (NMA) method, with the inclusion of prospective randomized control studies related to the treatment of EGFR-positive nonsquamous NSCLC, to compare the efficacy of various EGFR-TKIs. As of September 4, 2022, 16 studies on a total of 4180 patients were included. The retrieved literature was comprehensively evaluated as per the established inclusion and exclusion criteria, and valid data were extracted and included for analysis. RESULTS: The 6 treatment regimens included cetuximab, CTX (cyclophosphamide), icotinib, gefitinib, afatinib, and erlotinib. All of the 16 studies reported their findings about overall survival (OS), and 15 of them also reported findings about progression-free survival (PFS). The NMA results showed that there was no significant difference in OS among the 6 treatment regimens. It was observed that erlotinib had the highest likelihood of obtaining the best OS, followed by afatinib, gefitinib, icotinib, CTX, and cetuximab, in descending order. This indicates that the highest possibility of achieving the best OS was with erlotinib, while the lowest was with cetuximab. The NMA results also showed that the PFS achieved with treatment using afatinib, erlotinib, and gefitinib were all higher than that with treatment using CTX, with statistically significant differences. The results showed that there was no significant difference in PFS among erlotinib, gefitinib, afatinib, cetuximab, and icotinib. CTX, cetuximab, icotinib, gefitinib, afatinib, and erlotinib were ranked in descending order based on the PFS indicator SUCRA values, which implied that erlotinib had the highest possibility in achieving the best PFS, while CTX had the lowest. Discussion. EGFR-TKIs must be carefully selected for the treatment of different histologic subtypes of NSCLC. For EGFR mutation (+) nonsquamous NSCLC, erlotinib is most likely to achieve the best OS and PFS, which makes it the first choice in the formulation of a treatment plan.