Pemetrexed-Carboplatin Adjuvant Chemotherapy With or Without Gefitinib in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Harbouring EGFR Mutations: A Randomized, Phase II Study
Pemetrexed-Carboplatin Adjuvant Chemotherapy With or Without Gefitinib in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Harbouring EGFR Mutations: A Randomized, Phase II Study
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DOI：
10.1245/s10434-014-3586-9
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发表时间：
2014-06-01
影响因子：
3.7
通讯作者：
Wang, Si-Yu
中科院分区：
文献类型：
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作者：
Li, Ning;Ou, Wei;Wang, Si-Yu
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）在EGFR突变的晚期非小细胞肺癌（NSCLC）患者中显示出极大的疗效。吉非替尼在EGFR突变患者辅助化疗后的疗效和安全性尚不清楚。在这项开放标签的II期研究中，切除的携带EGFR突变的IIIA-N2期NSCLC患者（外显子19缺失或L 858 R点突变）随机分配接受培美曲塞治疗（500 mg/m2）和卡铂（AUC = 5），每21天给药一次，共4个周期，随后加或不加吉非替尼（250 mg/天），共6个月。主要终点为无病生存期（disease-free survival，DFS）。接受培美曲塞和卡铂（PC）-吉非替尼治疗的患者的DFS显著长于仅接受PC治疗的患者[风险比（HR），0.37; 95%置信区间（CI）0.16-0.85; P = 0.014;中位数，39.8 vs. 27.0个月]。PC-吉非替尼组和PC单药组的2年DFS率分别为78.9%和54.2%。PC-吉非替尼组和PC单药组的2年总生存率（OS）分别为92.4%和77.4%（HR，0.37; 95%CI 0.12-1.11，P = 0.076）。PC-吉非替尼组最常见的不良反应为皮疹（43.3%，13/30），化疗后给予吉非替尼耐受性良好，PC辅助治疗后给予吉非替尼可显著改善切除后携带EGFR突变的IIIA-N2期NSCLC患者的DFS。
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of gefitinib following adjuvant chemotherapy in patients with EGFR mutation are unknown.In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either exon 19 deletion or L858R point mutation) were assigned randomly to receive pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5), administered every 21 days for 4 cycles, followed with or without gefitinib (250 mg/day) for 6 months. The primary end point was disease-free survival (DFS).From August 2008 to September 2011, 60 patients were included in our center. DFS was significantly longer among those who received pemetrexed and carboplatin (PC)-gefitinib than among those who received PC alone [hazard ratio (HR), 0.37; 95 % confidence interval (CI) 0.16-0.85; P = 0.014; median, 39.8 vs. 27.0 months]. The rates of 2-year DFS were 78.9 % in the PC-gefitinib group and 54.2 % in the PC alone group. The rates of 2-year overall survival (OS) were 92.4 % in the PC-gefitinib group and 77.4 % in the PC alone group (HR, 0.37; 95 % CI 0.12-1.11, P = 0.076). The most common adverse event was rash (43.3 %, 13/30) in the PC-gefitinib group and the administration of gefitinib following chemotherapy was well tolerated.The administration of gefitinib following PC adjuvant therapy shows significant improvement in DFS in patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.