Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset
Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset
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DOI：
10.1093/jjco/hyx045
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发表时间：
2017-07-01
影响因子：
2.4
通讯作者：
Nishio, Makoto
中科院分区：
文献类型：
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作者：
Hida, Toyoaki;Satouchi, Miyako;Nishio, Makoto
ClinicalTrials.gov标识：NCT01685060。间变性淋巴瘤激酶(ALK)重排的非小细胞肺癌对酪氨酸激酶抑制剂敏感；然而，可能会产生耐药性。数据来自II期试验(ASSCEND-2)，评估了之前接受铂类化疗的日本ALK重排非小细胞肺癌患者的有效性和安全性，这些患者使用Crizotinib进行疾病进展。晚期ALK重排非小细胞肺癌患者，包括那些无症状或神经功能稳定的基线脑转移患者，每天口服Ceritinib 750 mg。全身和颅内反应由调查员和盲目独立审查委员会(RECIST v1.1)评估。安全性和耐受性也进行了调查。所有24名日本患者都接受了千分之二的先前治疗方案，其中克里佐替尼是在Ceritinib之前接受的最后一种治疗方案。Ceritinib暴露的中位持续时间为8.1个月(范围：0.2-12.5个月)。总有效率为45.8%(95%可信区间：25.6~67.2)。其他有效终点包括疾病控制率(79.2%[95%可信区间：57.8-92.9])、起效时间(中位数1.9个月[范围：1.7-3.5])、有效持续时间(中位数9.2个月[95%可信区间：4.0-不可估量])和无进展生存期(中位数6.6个月[95%可信区间：3.7-9.3])。在四名基线靶向脑病变活跃的患者中，两名患者的颅内部分反应(50%)。最常见的不良事件(大多数1/2级)是恶心(91.7%)、腹泻(83.3%)和呕吐(83.3%)。这项研究证明了在日本化疗和克里佐替尼预处理的ALK重排非小细胞肺癌患者中，Ceritinib的临床活性和可管理的耐受性，如整个Ascend-2研究人群所示。
ClinicalTrials.gov identifier: NCT01685060.Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer is sensitive to tyrosine kinase inhibitors; however, resistance can develop. Data are presented from the phase II trial (ASCEND-2) evaluating efficacy and safety in a subset of Japanese patients with ALK-rearranged non-small cell lung cancer previously treated with platinum-based chemotherapy, who experienced disease progression on crizotinib.Patients with advanced ALK-rearranged non-small cell lung cancer, including those with asymptomatic or neurologically stable baseline brain metastases, received oral ceritinib 750 mg/day. Whole-body and intracranial responses were assessed by investigator and Blinded Independent Review Committee (RECIST v1.1). Safety and tolerability were also investigated.All 24 Japanese patients had received a parts per thousand2 previous treatment regimens, with crizotinib the last therapy received prior to ceritinib. Median duration of ceritinib exposure was 8.1 (range: 0.2-12.5) months. Overall response rate was 45.8% (95% confidence interval: 25.6-67.2). Other efficacy endpoints included disease control rate (79.2% [95% confidence interval: 57.8-92.9]), time to response (median 1.9 months [range: 1.7-3.5]), duration of response (median 9.2 months [95% confidence interval: 4.0-not estimable]) and progression-free survival (median 6.6 months [95% confidence interval: 3.7-9.3]). Of the four patients with active baseline target brain lesions, two achieved an intracranial partial response (50%). The most commonly reported adverse events (majority grade 1/2) were nausea (91.7%), diarrhea (83.3%) and vomiting (83.3%).This study demonstrates the clinical activity and manageable tolerability of ceritinib in a Japanese subset of chemotherapy- and crizotinib-pretreated patients with ALK-rearranged non-small cell lung cancer who progressed on crizotinib, as was shown in the whole ASCEND-2 study population.ClinicalTrials.gov identifier: NCT01685060.