真实世界中表皮生长因子受体酪氨酸激酶抑制剂(吉非替尼或埃克替尼)在非小细胞肺癌患者术后辅助治疗中的临床疗效分析

The Clinical Efficacy of EGFR-TKIs (Gefitinib or Icotinib) in Adjuvant Therapy for Patients with NSCLC in the Real World

摘要: 目的：探讨接受第一代表皮生长因子受体酪氨酸激酶抑制剂(吉非替尼或埃克替尼)作为术后辅助治疗的非小细胞肺癌患者的预后以及影响预后的因素。方法：纳入2015-4月至2020-6月于我院胸外科行完全切除的表皮生长因子受体突变阳性的非小细胞肺癌患者，共纳入108名患者，43名接受埃克替尼作为辅助治疗，65名接受吉非替尼作为辅助治疗，主要研究目的为中位无病生存期、2年无病生存率以及药物相关不良反应发生率，次要研究目的为探究影响接受表皮生长因子受体酪氨酸激酶抑制剂作为辅助治疗的非小细胞肺癌患者的预后因素。结果：总体人群的中位无病生存期为42.7个月，接受吉非替尼治疗的患者中位无病生存期为41.2个月，接受埃克替尼治疗的患者中位无病生存期为42.7个月(p = 0.73; HR = 0.90 (0.49~1.65))，两组差异无统计学意义；2年无病生存率：86% vs 81% (p = 0.51; HR = 1.42 (0.50~4.03))，差异无统计学意义，吉非替尼相比于埃克替尼在不良反应发生率方面无统计学差异(70.8% vs 60.5%; p = 0.27)，19-Del相比于21-L858R中位无病生存期无统计学差异(42.7 vs 41.2; p = 0.28; HR = 1.39 (0.76~2.54))；有无肺气肿个人史以及有无恶性肿瘤家族史对接受表皮生长因子受体酪氨酸激酶抑制剂的患者预后无影响(41.9 vs 42.7; p = 0.68; HR = 1.16 (0.58~2.31))、(42.7 vs 41.9; p = 0.74; HR = 1.11 (0.52~2.09))。结论：在表皮生长因子受体突变阳性的完全切除的非小细胞肺癌患者中，与既往研究相比，接受表皮生长因子受体酪氨酸激酶抑制剂(吉非替尼或埃克替尼)治疗的患者相比于接受化疗的患者有更长的无病生存期，吉非替尼与埃克替尼相比在无病生存期以及药物不良反应发生率方面无统计学差异，推荐吉非替尼或埃克替尼应用于表皮生长因子受体突变阳性的完全切除的非小细胞肺癌患者的术后辅助治疗。

Abstract: Purpose: To investigate the clinical efficacy and prognostic factors in patients with NSCLC receiving first generation EGFR-TKIs (Gefitinib or Icotinib) as adjuvant therapy in the real world. Method: A total of 108 patients with EGFR mutation-positive (Exon 19-deletions or Exo-n 21-Leu858Arg) NSCLC who underwent R0 resection between April 2014 and June 2020 were included. 65 patients received gefitinib, and 43 patients received icotinib. Primary objectives were median disease-free survival, 2-year disease-free survival, and incidence of drug-related adverse reactions. Secondary objectives were to explore prognostic factors affecting patients with NSCLC who received epidermal growth factor receptor tyrosine kinase inhibitors as adjunctive therapy. Result: The median disease-free survival of a total of 108 patients was 42.7 months; Icotinib (n = 43) was non-inferior to gefitinib (n = 65) in terms of median disease-free survival (42.7 vs 41.2; p = 0.73; HR = 0.90 (0.49~1.65)); 2-year disease-free survival (DFS) rate was not statistically different (86% vs 81%; p = 0.51; HR = 1.42 (0.50~4.03)), as well as incidence rate of adverse events (70.8% vs 60.5%; p = 0.27). There was no statistical difference between Exon 19-deletions and Exon 21-Leu 858 Arg in median disease free survival (42.7 vs 41.2; p = 0.28; HR = 1.39 (0.76~2.54)); emphysema and family history of malignancy had no effect on the prognosis in patients receiving EGFR-TKIs as adjuvant therapy with NS-CLC (41.9 vs 42.7; p = 0.68; HR = 1.16 (0.58~2.31)), (42.7 vs 41.9; p = 0.74; HR = 1.11 (0.52~2.09)). Conclusion: In patients with EGFR mutation-positive NSCLC who underwent R0 resection, compared with previous studies whose patients received standard chemotherapy, patients who received gefitinib or icotinib as adjuvant therapy had longer disease-free survival, and there was no statistical difference in patients receiving gefitinib or icotinib in terms of disease-free survival and Incidence rate of adverse events. It is recommended that gefitinib or icotinib be used as adjuvant therapy in patients with EGFR mutation-positive NSCLC who underwent R0 resection.