Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases globally and most patients receive their diagnosis at advanced or metastatic disease stages. The use of tyrosine kinase inhibitors (TKIs) such as erlotinib (first-generation) and osimertinib (third-generation) to treat NSCLC is possible because of activating mutations in the epidermal growth factor receptor (EGFR). Although osimertinib has shown better results in recent trials, direct and updated comparisons with erlotinib, especially in combination regimens, are still limited.Background/Objectives: This study aimed to compare the efficacy and safety of osimertinib versus erlotinib, both as monotherapies and in combination, in treatment-naïve patients with advanced or metastatic EGFR-mutated NSCLC.Methods: A systematic review and network meta-analysis were conducted following PRISMA-NMA guidelines and registered in PROSPERO (CRD42025649761). PubMed, EMBASE, and Scopus were searched up to February 2025 for randomized controlled trials (RCTs) that compared erlotinib- or osimertinib-based regimens in previously untreated EGFR-mutated advanced NSCLC. Outcomes included overall survival (OS), progression-free survival (PFS), and grade ≥ 3 adverse events. A frequentist random-effects model was used, and treatments were ranked using p-scores.Results: Eleven RCTs (2341 patients) were included. Osimertinib, alone or with chemotherapy, resulted in significantly longer OS compared to erlotinib-based regimens (HR for OS vs. erlotinib: 1.59, 95% CI 1.09–2.31). All osimertinib and erlotinib regimens outperformed chemotherapy for PFS, but no statistically significant differences were observed between osimertinib and erlotinib. Severe adverse events were comparable, though osimertinib ranked highest for safety. The combination of osimertinib with chemotherapy achieved the highest p-scores for both OS and PFS.Conclusions: Osimertinib is associated with superior overall survival and comparable safety versus erlotinib-based strategies in first-line treatment of advanced EGFR-mutated NSCLC. These findings reinforce osimertinib as the preferred first-line option in this setting.
非小细胞肺癌（NSCLC）占全球肺癌病例的85%，大多数患者在疾病晚期或转移阶段才获得诊断。由于表皮生长因子受体（EGFR）存在激活突变，使用酪氨酸激酶抑制剂（TKI）如厄洛替尼（第一代）和奥希替尼（第三代）治疗NSCLC成为可能。尽管近期试验显示奥希替尼疗效更优，但其与厄洛替尼的直接且更新的对比研究，尤其是在联合治疗方案中，仍然有限。 **背景/目的：** 本研究旨在比较奥希替尼与厄洛替尼，无论是作为单药治疗还是联合治疗，在未经治疗的晚期或转移性EGFR突变NSCLC患者中的疗效和安全性。 **方法：** 本研究遵循PRISMA-NMA指南进行了系统综述和网状荟萃分析，并在PROSPERO注册（注册号CRD42025649761）。检索了截至2025年2月的PubMed、EMBASE和Scopus数据库，查找比较基于厄洛替尼或奥希替尼方案用于既往未经治疗的EGFR突变晚期NSCLC的随机对照试验（RCT）。结局指标包括总生存期（OS）、无进展生存期（PFS）以及≥3级不良事件。采用频率学随机效应模型进行分析，并使用p值排序对治疗方案进行排序。 **结果：** 共纳入11项RCT（2341例患者）。与基于厄洛替尼的方案相比，奥希替尼（无论是单药还是联合化疗）均能显著延长OS（OS的HR vs. 厄洛替尼：1.59，95% CI 1.09–2.31）。所有奥希替尼和厄洛替尼方案在PFS方面均优于化疗，但奥希替尼与厄洛替尼之间未观察到统计学显著差异。严重不良事件发生率相当，但奥希替尼在安全性方面排名最高。奥希替尼联合化疗方案在OS和PFS方面均获得了最高的p值排序。 **结论：** 在晚期EGFR突变NSCLC的一线治疗中，与基于厄洛替尼的策略相比，奥希替尼具有更优的总生存期和相当的安全性。这些发现进一步支持奥希替尼作为该情况下的首选一线治疗方案。
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