Anaplastic Lymphoma Kinase Translocation A Predictive Biomarker of Pemetrexed in Patients with Non-small Cell Lung Cancer
Anaplastic Lymphoma Kinase Translocation A Predictive Biomarker of Pemetrexed in Patients with Non-small Cell Lung Cancer
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DOI：
10.1097/jto.0b013e3182208fc2
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发表时间：
2011-09-01
影响因子：
20.4
通讯作者：
Bang, Yung-Jue
中科院分区：
文献类型：
--
作者：
Lee, Jeong-Ok;Kim, Tae Min;Bang, Yung-Jue
简介：本研究比较了培美曲塞在间变性淋巴瘤激酶（ALK）阳性与ALK阴性患者中的疗效（表皮生长因子受体[EGFR]突变体或ALK和EGFR的野生型[WT]）非小细胞肺癌（NSCLC）。接受第二次-在首尔国立大学医院，对2007年3月至2010年4月期间培美曲塞及更高剂量培美曲塞治疗线的患者进行EGFR突变和ALK重排筛查。培美曲塞的临床和体外疗效进行了评估，为每个基因型group.Results：95例NSCLC患者的基因分型如下：43（45%）EGFR突变，15（16%）ALK易位，和37（39%）WT。ALK易位患者的总体缓解率上级优于EGFR突变或WT患者（46.7 vs 4.7 vs 16.2%，p = 0.001）。ALK阳性患者的至进展时间长于EGFR突变或WT患者（9.2 vs 1.4 vs 2.9个月，p = 0.001）。单独ALK阳性是总缓解率（风险比[HR] = 0.07，95%置信区间[CI]：0.01-0.32; p = 0.001）和至疾病进展时间（HR = 0.44，95% CI：0.24-0.80; p = 0.007）的显著预测因子。无论治疗线如何，ALK阳性均保持独立显著性（HR = 0.43，95% CI：0.24-0.77; p = 0.005）。结论：培美曲塞对ALK阳性NSCLC患者有较好的治疗作用。ALK阳性可独立预测培美曲塞在NSCLC患者中的疗效。
Introduction: This study compared the efficacy of pemetrexed in patients with anaplastic lymphoma kinase (ALK)-positive versus ALK-negative (epidermal growth factor receptor [EGFR] mutant or wild type [WT] for both ALK and EGFR) non-small cell lung cancer (NSCLC).Methods: Patients with advanced NSCLC who received second-line pemetrexed and beyond between March 2007 and April 2010 were screened for EGFR mutations and ALK rearrangements at Seoul National University Hospital. The clinical and in vitro efficacy of pemetrexed was evaluated for each genotypic group.Results: Ninety-five NSCLC patients were genotyped as follows: 43 (45%) EGFR mutation, 15 (16%) ALK translocation, and 37 (39%) WT. The overall response rate was superior in ALK-translocated patients compared with EGFR mutant or WT patients (46.7 versus 4.7 versus 16.2%, p = 0.001). ALK-positive patients showed longer time to progression than EGFR mutant or WT patients (9.2 versus 1.4 versus 2.9 months, p = 0.001). ALK positivity alone was a significant predictor for overall response rate (hazard ratio [HR] = 0.07, 95% confidence interval [CI]: 0.01-0.32; p = 0.001) and time to progression (HR = 0.44, 95% CI: 0.24-0.80; p = 0.007). ALK positivity remained independently significant regardless of treatment line (HR = 0.43, 95% CI: 0.24-0.77; p = 0.005). Thymidylate synthase mRNA levels in ALK-positive cells were significantly lower compared with control cells (p < 0.05).Conclusion: Pemetrexed is an effective treatment in patients with ALK-positive NSCLC. ALK positivity was independently predictive of pemetrexed efficacy in NSCLC patients.