He Qihua, Liu Jun, Cai Xiuyu, He Miao, Li Caichen, Liang Hengrui, Cheng Bo, Xia Xiaojun, Guo Minzhang, Liang Peng, Zhong Ran, Li Feng, Yu Ziwen, Zhao Yi, Ou Limin, Xiong Shan, Li Jianfu, Zhang Jianrong, He Jianxing, Liang Wenhua
Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.
Transl Lung Cancer Res. 2021 Nov;10(11):4120-4129. doi: 10.21037/tlcr-21-649.
Several randomized controlled trials have suggested that adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were associated with prolonged disease-free survival (DFS) in EGFR-mutated NSCLC patients after radical resection, comparing with chemotherapy or placebo. We aimed to compare the effectiveness of different first-generation EGFR-TKIs as adjuvant treatment in real-world setting.
Early-stage EGFR mutated NSCLC patients who underwent radical resection and treated with first-generation EGFR-TKIs (gefitinib, erlotinib, icotinib) as adjuvant therapy between Feb 2010 and Jan 2019 were retrieved from a prospectively-maintained database in our center. The primary endpoint was DFS in stage II/III (TNM 8th) patients with exploratory endpoint regarding DFS in stage I patients. Sensitivity analyses were based on propensity score matched (PSM) cohorts. Treatment failure patterns among different TKIs were also compared.
Of 588 eligible patients, 198 patients (33.7%) received gefitinib, 106 patients (17.9%) received erlotinib, and 284 patients (48.2%) received icotinib. The median DFS of stage II/III patients in the gefitinib, erlotinib and icotinib group were 36.1 months (95% CI, 23.9-49.4), 42.8 months (95% CI, 29.6-97.8), and 32.5 months (95% CI, 23.9-49.4), respectively, with no significant difference (log-rank test P=0.22). There was also no significant difference in DFS among stage I patients receiving different TKIs (P=0.12). PSM adjustments and multivariate analyses adjusting for other confounders revealed similar results. In addition, there were no significant differences in treatment failure pattens in different EGFR-TKI arms, especially in terms of brain metastases (6.1% in gefitinb, 7.5% in erlotinib, 3.9% in icotinib) and bone metastases (8.6% in gefitinb, 9.4% in erlotinib, 7.0% in icotinib).
This first and largest real-world study showed that gefitinib, erlotinib, and icotinib demonstrated comparable clinical effectiveness as adjuvant therapy for patients with early-stage EGFR mutated NSCLC.
多项随机对照试验表明，与化疗或安慰剂相比，辅助性表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）可延长EGFR突变的非小细胞肺癌（NSCLC）患者根治性切除术后的无病生存期（DFS）。我们旨在比较不同第一代EGFR-TKIs在真实世界中作为辅助治疗的有效性。
从我们中心一个前瞻性维护的数据库中检索出2010年2月至2019年1月期间接受根治性切除并接受第一代EGFR-TKIs（吉非替尼、厄洛替尼、埃克替尼）作为辅助治疗的早期EGFR突变NSCLC患者。主要终点是II/III期（TNM第8版）患者的DFS，探索性终点是I期患者的DFS。敏感性分析基于倾向评分匹配（PSM）队列。还比较了不同TKIs之间的治疗失败模式。
在588例符合条件的患者中，198例（33.7%）接受吉非替尼治疗，106例（17.9%）接受厄洛替尼治疗，284例（48.2%）接受埃克替尼治疗。吉非替尼、厄洛替尼和埃克替尼组II/III期患者的中位DFS分别为36.1个月（95%CI，23.9-49.4）、42.8个月（95%CI，29.6-97.8）和32.5个月（95%CI，23.9-49.4），差异无统计学意义（对数秩检验P=0.22）。接受不同TKIs治疗的I期患者的DFS也无显著差异（P=0.12）。PSM调整和对其他混杂因素进行调整的多变量分析显示了相似的结果。此外，不同EGFR-TKI组的治疗失败模式无显著差异，尤其是在脑转移（吉非替尼组为6.1%，厄洛替尼组为7.5%，埃克替尼组为3.9%）和骨转移（吉非替尼组为8.6%，厄洛替尼组为9.4%，埃克替尼组为7.0%）方面。
这项首次也是最大规模的真实世界研究表明，吉非替尼、厄洛替尼和埃克替尼作为早期EGFR突变NSCLC患者的辅助治疗，显示出相当的临床疗效。
