Yin Jianqiong, Huang Jing, Ren Min, Tang Rui, Xie Linshen, Xue Jianxin
Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
Cancer Pathog Ther. 2024 Jun 21;3(2):135-146. doi: 10.1016/j.cpt.2024.06.004. eCollection 2025 Mar.
To date, no direct comparisons have been performed to compare the effectiveness of all epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) against mutation-positive non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of EGFR-TKIs in patients with mutation-positive NSCLC.
We conducted a network meta-analysis of randomized controlled trials comparing osimertinib, lazertinib, aumolertinib, befotertinib, furmonertinib, dacomitinib, afatinib, erlotinib, gefitinib, icotinib, and chemotherapy. Pooled estimations of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity (grade ≥ 3 adverse events) were performed within the Bayesian framework.
Twenty-three trials involving 11 treatments were included. All EGFR-TKIs improved PFS relative to chemotherapy, except for icotinib (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.26-1.44). All EGFR-TKIs demonstrated significant ORR benefits over chemotherapy. Osimertinib seemed to prolong PFS compared with icotinib (HR = 0.29, 95% CI: 0.1-0.86), gefitinib (HR = 0.39, 95% CI: 0.21-0.74), and erlotinib (HR = 0.53, 95% CI: 0.29-1.0). In addition, osimertinib showed favorable superiority in improving OS compared with chemotherapy (HR = 0.6, 95% CI: 0.43-0.82), gefitinib (HR = 0.61, 95% CI: 0.45-0.83), erlotinib (HR = 0.65, 95% CI: 0.48-0.89), and afatinib (HR = 0.65, 95% CI: 0.44-0.94). Among these regimens, afatinib showed the highest ORR (cumulative probability: 96.96%). Icotinib was associated with minimal toxicity among the EGFR-TKIs, followed by furmonertinib and osimertinib. Moreover, the toxicity spectra differed among the EGFR-TKIs. Subgroup analyses of patients with two common types of mutations indicated that furmonertinib possessed the greatest PFS benefit in patients with exon 19 deletion, and lazertinib showed the greatest PFS benefit in patients with Leu858Arg mutation. We also identified differences between EGFR-TKIs in prolonging PFS in patients with brain metastasis.
Osimertinib is the first choice of treatment with considerable efficacy and safety for mutation-positive NSCLC. The treatments associated with the best PFS in patients with exon 19 deletions and Leu858Arg mutations were furmonertinib and lazertinib, respectively.
迄今为止，尚未进行直接比较所有表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗突变阳性非小细胞肺癌（NSCLC）有效性的研究。本研究旨在探讨EGFR-TKIs治疗突变阳性NSCLC患者的疗效和安全性。
我们对比较奥希替尼、拉泽替尼、奥莫替尼、贝福替尼、伏美替尼、达可替尼、阿法替尼、厄洛替尼、吉非替尼、埃克替尼和化疗的随机对照试验进行了网状荟萃分析。在贝叶斯框架内对无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）和毒性（≥3级不良事件）进行汇总估计。
纳入了涉及11种治疗方法的23项试验。除埃克替尼外（风险比[HR]=0.61，95%置信区间[CI]：0.26-1.44），所有EGFR-TKIs相对于化疗均改善了PFS。所有EGFR-TKIs在ORR方面均显示出优于化疗的显著效果。与埃克替尼（HR=0.29，95%CI：0.1-0.86）、吉非替尼（HR=0.39，95%CI：0.21-0.74）和厄洛替尼（HR=0.53，95%CI：0.29-1.0）相比，奥希替尼似乎能延长PFS。此外，与化疗（HR=0.6，95%CI：0.43-0.82）、吉非替尼（HR=0.61，95%CI：0.45-0.83）、厄洛替尼（HR=0.65，95%CI：0.48-0.89）和阿法替尼（HR=0.65，95%CI：0.44-0.94）相比，奥希替尼在改善OS方面显示出良好的优势。在这些治疗方案中，阿法替尼的ORR最高（累积概率：96.96%）。在EGFR-TKIs中，埃克替尼的毒性最小，其次是伏美替尼和奥希替尼。此外，EGFR-TKIs的毒性谱有所不同。对两种常见类型突变患者的亚组分析表明，伏美替尼在19外显子缺失患者中PFS获益最大，拉泽替尼在Leu858Arg突变患者中PFS获益最大。我们还发现EGFR-TKIs在延长脑转移患者PFS方面存在差异。
奥希替尼是治疗突变阳性NSCLC疗效和安全性俱佳的首选药物。对于19外显子缺失和Leu858Arg突变患者，分别与最佳PFS相关的治疗药物是伏美替尼和拉泽替尼。
