Background First-line treatments for nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations have been evaluated in various clinical trials. However, it remains unclear which is the optimal treatment. Methods A Bayesian network meta-analysis was used to assess the efficacy and safety profile of gefitinib, erlotinib, afatinib, dacomitinib, osimertinib, erlotinib plus bevacizumab and pemetrexed/carboplatin, or pemetrexed alone plus gefitinib. Literature was sourced from electronic databases. Data regarding objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs), treatment-related adverse event grades 3-5 (TRAE 3-5), specific TRAEs [diarrhea, rash, and elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT)] were extracted. The regimens were then ranked using the surface under the cumulative ranking curve (SUCRA). Results A total of 19 studies involving 4607 EGFR-mutant NSCLC patients were analyzed. In regards to efficacy, pemetrexed/carboplatin (PC) plus gefitinib was superior in ORR and OS to chemotherapy and first-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). All the TKI-based regimens had equivalent DCR and PFS. Patients with the L858R mutation treated with PC plus gefitinib achieved a better outcome than most EGFR TKI-related groups (except osimertinib) in the PFS subgroup. In regards to safety, no statistical significance for TRAEs was observed among the eight treatments. In regards to SUCRA, PC plus gefitinib ranked first in terms of PFS, OS, and TRAE grades 3-5. Conclusions Pemetrexed/carboplatin plus gefitinib is a promising treatment option for EGFR-mutant NSCLC patients in the first-line setting.

中文翻译：

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培美曲塞/卡铂加吉非替尼作为 EGFR 突变晚期非小细胞肺癌的一线治疗：贝叶斯网络荟萃分析。

背景 已在各种临床试验中评估了具有表皮生长因子受体 (EGFR) 突变的非小细胞肺癌 (NSCLC) 的一线治疗方法。然而，目前尚不清楚哪种是最佳治疗方法。方法 使用贝叶斯网络荟萃分析评估吉非替尼、厄洛替尼、阿法替尼、达克替尼、奥希替尼、厄洛替尼加贝伐单抗和培美曲塞/卡铂或单独培美曲塞加吉非替尼的疗效和安全性。文献来自电子数据库。关于客观缓解率 (ORR)、疾病控制率 (DCR)、无进展生存期 (PFS)、总生存期 (OS)、治疗相关不良事件 (TRAE)、治疗相关不良事件 3-5 级 (TRAE) 的数据3-5)，特定的 TRAE [腹泻、皮疹、和升高的天冬氨酸氨基转移酶/丙氨酸氨基转移酶 (AST/ALT)] 被提取。然后使用累积排序曲线下的表面 (SUCRA) 对方案进行排序。结果共分析了 19 项研究，涉及 4607 名 EGFR 突变的 NSCLC 患者。在疗效方面，培美曲塞/卡铂 (PC) 加吉非替尼在 ORR 和 OS 方面优于化疗和第一代 EGFR-酪氨酸激酶抑制剂 (EGFR-TKI)。所有基于 TKI 的方案都具有相同的 DCR 和 PFS。在 PFS 亚组中，接受 PC 加吉非替尼治疗的 L858R 突变患者比大多数 EGFR TKI 相关组（奥希替尼除外）取得了更好的结果。在安全性方面，在八种治疗中未观察到 TRAE 的统计学意义。在 SUCRA 方面，PC 加吉非替尼在 PFS、OS、和 TRAE 等级 3-5。结论培美曲塞/卡铂加吉非替尼是一线治疗 EGFR 突变 NSCLC 患者的一种有前景的治疗选择。