Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study.
Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study.
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DOI：
10.1093/annonc/mdy121
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发表时间：
2018-06-01
期刊：
影响因子：
--
通讯作者：
Wolf J
中科院分区：
文献类型：
--
作者：
Novello S;Mazières J;Oh IJ;de Castro J;Migliorino MR;Helland Å;Dziadziuszko R;Griesinger F;Kotb A;Zeaiter A;Cardona A;Balas B;Johannsdottir HK;Das-Gupta A;Wolf J
这是第一次直接比较阿莱替尼与标准化疗在晚期/转移性间变性淋巴瘤激酶(ALK)阳性的非小细胞肺癌(NSCLC)患者中的有效性和安全性的试验，这些患者已经进展或对Crizotinib不耐受。ALUR(MO29750；NCT02604342)是一项随机、多中心、开放标签的III期试验，在晚期/转移性ALK阳性的非小细胞肺癌患者中进行阿莱替尼与化疗的对比试验，这些患者以前接受过铂类双重化疗和Crizotinib治疗。患者按2：1随机比例接受阿莱替尼600 mg每日两次或化疗(培美曲塞500 mg/m2或多西紫杉醇75 mg/m2，每3 周一次)，直到疾病进展、死亡或停药。主要终点是研究者评估的无进展生存期(PFS)。总共有107名患者在欧洲和亚洲的13个国家和地区被随机分组(阿莱替尼，n = 72；化疗n = 35)。研究者评估的中位PFS分别为9.6 月[95%可信区间：6.9-12.2]和1.4 月(95%可信区间：1.3-1.6)[风险比(HR)0.15(95%可信区间：0.08-0.29)；P <； 0.001]。独立审查委员会评估的阿莱替尼的PFS也显著延长[HR0.32(95%CI：0.17-0.59)；使用阿莱替尼的中位PFS为7.1 月(95%CI：6.3-10.8)，使用化疗的PFS为1.6 月(95%CI：1.3-4.1)]。在基线可测量的中枢神经系统疾病患者(阿莱替尼，n = 24；化疗，n = 16)中，阿莱替尼的中枢神经系统客观有效率(54.2%)显著高于化疗(0%；P <； 0.001)。化疗组≥3级不良反应发生率(41.2%)高于阿莱替尼组(27.1%)。尽管阿莱替尼治疗持续时间较长(20.1 周比6.0 周)，但阿莱替尼组导致研究药物停用的不良反应发生率(5.7%)低于化疗组(8.8%)。与化疗相比，阿莱替尼显著改善了接受Crizotinib预治疗的ALK阳性非小细胞肺癌患者的全身和中枢神经系统疗效，具有良好的安全性。ClinicalTrials.gov NCT02604342；罗氏研究MO29750
This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib. ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS). Altogether, 107 patients were randomized (alectinib, n = 72; chemotherapy, n = 35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months [95% confidence interval (CI): 6.9–12.2] with alectinib and 1.4 months (95% CI: 1.3–1.6) with chemotherapy [hazard ratio (HR) 0.15 (95% CI: 0.08–0.29); P < 0.001]. Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17–0.59); median PFS was 7.1 months (95% CI: 6.3–10.8) with alectinib and 1.6 months (95% CI: 1.3–4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001). Grade ≥3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 weeks versus 6.0 weeks). Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile. ClinicalTrials.gov NCT02604342; Roche study MO29750
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影响因子：
158.5
作者：
Solomon, Benjamin J.;Mok, Tony;Waqar, S.
通讯作者：
Waqar, S.
影响因子：
158.5
作者：
Peters, Solange;Camidge, D. Ross;Mok, Tony
通讯作者：
Mok, Tony
ALECTINIB在ALK阳性，抗克唑替尼，非小细胞肺癌：单组，多中心，第二阶段试验中。
DOI：
10.1016/s1470-2045(15)00488-x
发表时间：
2016-02
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Shaw AT;Gandhi L;Gadgeel S;Riely GJ;Cetnar J;West H;Camidge DR;Socinski MA;Chiappori A;Mekhail T;Chao BH;Borghaei H;Gold KA;Zeaiter A;Bordogna W;Balas B;Puig O;Henschel V;Ou SI;study investigators
通讯作者：
study investigators
影响因子：
51.1
作者：
Shaw, Alice T.;Kim, Tae Min;Felip, Enriqueta
通讯作者：
Felip, Enriqueta
影响因子：
45.3
作者：
Costa, Daniel B.;Shaw, Alice T.;Crino, Lucio
通讯作者：
Crino, Lucio