Combined Survival Analysis of Prospective Clinical Trials of Gefitinib for Non-Small Cell Lung Cancer with EGFR Mutations
Combined Survival Analysis of Prospective Clinical Trials of Gefitinib for Non-Small Cell Lung Cancer with EGFR Mutations
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DOI：
10.1158/1078-0432.ccr-09-0391
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发表时间：
2009-07-01
影响因子：
11.5
通讯作者：
Nukiwa, Toshihiro
中科院分区：
文献类型：
--
作者：
Morita, Satoshi;Okamoto, Isamu;Nukiwa, Toshihiro
目的：表皮生长因子受体（EGFR）基因的体细胞突变与非小细胞肺癌患者对吉非替尼的反应增加相关。我们研究了吉非替尼对EGFR突变阳性非小细胞肺癌患者的无进展生存期和总生存期的影响。实验设计：我们搜索了所有前瞻性评价吉非替尼对日本EGFR突变晚期非小细胞肺癌疗效的临床试验。结果：共纳入7项符合条件的试验，共纳入148例EGFR突变的非小细胞肺癌患者。吉非替尼的总体缓解率为76.4% [95%置信区间（95%CI），69.5-83.2]。中位无进展生存期和总生存期分别为9.7个月（95%CI，8.2-11.1）和24.3个月（95%CI，19.8-28.2）。良好的体能状态和化疗初治状态与较长的无进展生存期或总生存期显著相关。在148例患者中，87例接受吉非替尼作为一线治疗，而61例在吉非替尼治疗前接受全身化疗。吉非替尼优先治疗组在一线治疗开始后的中位无进展生存期明显长于化疗优先治疗组（10.7个月对6.0个月; P < 0.001），而两组之间的中位总生存期无明显差异结论：吉非替尼单药治疗在EGFR突变的非小细胞肺癌患者的无进展生存期和总生存期方面具有显著的临床获益。在这些患者中，有必要进行比较化疗与吉非替尼作为一线治疗的随机试验。
Purpose: Somatic mutations of the epidermal growth factor receptor (EGFR) gene are associated with an increased response to gefitinib in patients with non-small cell lung cancer. We have examined the impact of gefitinib on progression-free survival and overall survival in patients with EGFR mutation - positive non - small cell lung cancer.Experimental Design: We searched for all clinical trials that prospectively evaluated the efficacy of gefitinib for advanced non - small cell lung cancer with EGFR mutations in Japan. We did a combined analysis based on individual patient data from the identified trials.Results: Seven eligible trials were identified fora total of 148 non - small cell lung cancer patients with EGFR mutations. The overall response rate to gefitinib was 76.4% [95% confidence interval (95% CI), 69.5-83.2]. The median progression-free survival and overall survival were 9.7 months (95% CI, 8.2-11.1) and 24.3 months (95% CI, 19.8-28.2), respectively. Good performance status and chemotherapy-naive status were significantly associated with a longer progression-free survival or overall survival. Of the 148 patients, 87 received gefitinib as a first-line therapy, whereas 61 received systemic chemotherapy before gefitinib treatment. The median progression-free survival after the start of first-line therapy was significantly longer in the gefitinib-first group than in the chemotherapy-first group (10.7 versus 6.0 months; P < 0.001), whereas no significant difference in median overall survival was apparent between the two groups (27.7 versus 25.7 months; P = 0.782).Conclusions: Gefitinib monotherapy confers substantial clinical benefit in terms of progression-free survival and overall survival in non-small cell lung cancer patients with EGFR mutations. Randomized trials comparing chemotherapy with gefitinib as a first-line treatment are warranted in such patients.