Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK-Positive Non-Small-Cell Lung Cancer: AF-001JP.
Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK-Positive Non-Small-Cell Lung Cancer: AF-001JP.
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DOI：
10.1200/jco.2016.70.5749
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发表时间：
2017-05-10
期刊：
影响因子：
--
通讯作者：
Nishio M
中科院分区：
文献类型：
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作者：
Tamura T;Kiura K;Seto T;Nakagawa K;Maemondo M;Inoue A;Hida T;Yoshioka H;Harada M;Ohe Y;Nogami N;Murakami H;Kuriki H;Shimada T;Tanaka T;Takeuchi K;Nishio M
阿莱替尼是一种间变性淋巴瘤激酶(ALK)特异性激酶抑制剂，似乎对具有各种ALK突变的非小细胞肺癌(NSCLC)有效。对AF-001JP的初步分析报告了一个有希望的总体应答率。为了评估无进展生存期(PFS)和总生存期(OS)，对AF-001JP II期患者进行了大约3年的随访。口服阿莱替尼300毫克，每天两次，用于ALK抑制剂--幼稚的、ALK阳性的NSCLC患者，这些患者在之前的一种或多种化疗方案后病情恶化。在这一长期随访中，评估了疗效(PFS，OS)、肿瘤缩小与PFS的相关性、阿来替尼的安全性以及癌症症状的缓解。在更新的数据截止日期(2015年9月10日；第一名患者在2011年8月30日，最后一名患者在2012年4月18日)，46名II期患者中有25名仍在接受阿莱替尼治疗。18名患者(39%)证实了疾病进展；中位数PFS未达到(3年PFS率，62%；95%可信区间，45至75)。14名患者在基线时有脑转移；其中6名患者仍在研究中，没有中枢神经系统和全身进展。肿瘤缩小与PFS无相关性。3年OS率为78%(13个事件)。最常见的治疗相关不良事件(所有级别)是血胆红素升高(36.2%)。在阿来替尼治疗期间，大多数癌症症状都得到了早期缓解，治疗症状的药物显著减少。阿莱替尼在这3年的随访中是有效的，在没有接受过ALK抑制剂治疗的情况下，长期给药对ALK阳性的NSCLC具有良好的安全性。
Alectinib is an anaplastic lymphoma kinase (ALK) –specific kinase inhibitor that seems to be effective against non–small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor–naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.