Clinical outcome for EML4-ALK-positive patients with advanced non-small-cell lung cancer treated with first-line platinum-based chemotherapy
Clinical outcome for EML4-ALK-positive patients with advanced non-small-cell lung cancer treated with first-line platinum-based chemotherapy
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DOI：
10.1093/annonc/mds124
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发表时间：
2012-11-01
影响因子：
50.5
通讯作者：
Nakagawa, K.
中科院分区：
文献类型：
--
作者：
Takeda, M.;Okamoto, I.;Nakagawa, K.
EML4-ALK融合癌基因是最近在非小细胞肺癌(NSCLC)患者亚群中发现的一个分子靶点。然而，关于未接受ALK激酶抑制剂治疗的EML4-ALK阳性晚期NSCLC患者的一线铂类化疗结果的数据有限。对携带EML4-ALK的晚期非鳞状细胞肺癌患者与携带EGFR突变和无分子异常的晚期非鳞状细胞肺癌患者进行了以铂为基础的化疗疗效比较。在200名晚期非鳞状细胞肺癌患者中，18例(9.0%)EML4-ALK阳性，31例(15.5%)携带EGFR突变，151例(75.5%)为野生型。以铂为基础的联合化疗在EML4-ALK、EGFR突变和野生型队列中显示出类似的疗效，在缓解率和无进展生存率方面，EML4-ALK队列的总体生存率与野生型队列非常相似。在EML4-ALK队列中，融合基因变异体1或3的患者占主导地位，他们对铂类药物的敏感性没有差异。如果不进行有效的靶向治疗，EML4-ALK阳性的晚期非小细胞肺癌患者表现出与野生型肿瘤相似的侵袭性临床过程。
The EML4-ALK fusion oncogene represents a recently identified molecular target in a subset of patients with non-small-cell lung cancer (NSCLC). Limited data have been available, however, on the outcome of first-line platinum-based chemotherapy in patients with EML4-ALK-positive advanced NSCLC who have not been treated with an ALK kinase inhibitor.The efficacy of platinum-based chemotherapy was compared between patients with advanced nonsquamous NSCLC who harbor EML4-ALK and those who harbor EGFR mutations and those with neither molecular abnormality.Among 200 patients with advanced nonsquamous NSCLC, 18 (9.0%) were positive for EML4-ALK, 31 (15.5%) harbored EGFR mutations, and 151 (75.5%) were wild type for both abnormalities. Platinum-based combination chemotherapy showed similar efficacies in the EML4-ALK, EGFR mutation, and wild-type cohorts in terms of response rate and progression-free survival, and overall survival in the EML4-ALK cohort closely resembled that in the wild-type cohort. Within the EML4-ALK cohort, patients with variants 1 or 3 of the fusion gene were predominant and did not appear to differ in their sensitivity to the platinum-based regimens.Patients with EML4-ALK-positive advanced NSCLC manifest an aggressive clinical course similar to that of those with wild-type tumors if the effective targeted therapy is not instituted.