新英格兰医学杂志:ALEX 试验证实罗氏新药艾乐替尼治疗肺癌优于克唑替尼_印度特罗凯价钱

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新英格兰医学杂志:ALEX 试验证实罗氏新药艾乐替尼治疗肺癌优于克唑替尼_印度特罗凯价钱

新英格兰医学杂志》2017年6月6日在线先发

http://www.nejm.org/doi/full/10.1056/NEJMoa1704795

在未治疗过的ALK阳性非小细胞肺癌中艾乐替尼对比克唑替尼

背景

艾乐替尼(alectinib)是一种高度选择性的间变性淋巴瘤激酶(ALK)抑制剂,在ALK阳性非小细胞肺癌的治疗中已显示出全身性及中枢神经系统(CNS)的疗效。在既往未治疗过的晚期ALK阳性非小细胞肺癌患者中,这些患者包括无症状的中枢神经系统转移患者,我们对艾乐替尼与克唑替尼相比较,进行了研究。

方法

在一项随机化、开放标签的3期临床试验中,我们随机入组了303例既往未经治疗的晚期ALK阳性非小细胞肺癌患者,接受艾乐替尼(600mg,每日两次)或克唑替尼(250mg,每日两次)。主要终点是研究者评估的无进展生存期。次要终点是独立审查委员会评估的无进展生存期、出现中枢神经系统进展的时间、客观反应率及总生存期。

结果

克唑替尼组中位随访期17.6月、艾乐替尼组18.6月,随访期间,艾乐替尼组152名患者中有62例(41%)发生肿瘤进展或者死亡事件,克唑替尼组151名患者中有102例(68%)。研究者评估的无进展生存期艾乐替尼组明显高于克唑替尼组(艾乐替尼组12个月无进展事件生存率68.4%[95%置信区间CI,61.0-75.9],对比克唑替尼组48.7%[95%CI,40.4-56.9],疾病进展或死亡的风险比0.47[95%CI,0.34-0.65],P<0.001);艾乐替尼组中位无进展生存期尚未达到。独立评审委员会评估的无进展生存期结果与主要终点结果一致。艾乐替尼组共计18名患者(12%)发生了中枢神经系统进展事件,与之相比,克唑替尼组有68名(45%)(病因特异性风险比,0.16;95%CI,0.10-0.28;P<0.001)。艾乐替尼组126名患者治疗有效(反应率,82.9%;95%CI,76.0-88.5),克唑替尼组有114名(反应率,75.5%;95%CI,67.8-82.1)(P=0.09)。艾乐替尼组3至5级不良反应较少(41%对比克唑替尼组50%)。

结论

在ALK阳性非小细胞肺癌的初始治疗中,与克唑替尼相比,艾乐替尼表现出更好的疗效、更低的毒性。

《壹篇》李晓爽

ALK重排肺癌:克唑替尼与艾乐替尼序贯治疗获益最大

克唑替尼作为ALK重排非小细胞肺癌一线用药从2011左右年来一直占据一线用药的王者地位,屹立不倒! 艾乐替尼作为二线药物批准上市后,取得了不错的业绩,在两个促进艾乐替尼获批的临床研究中,出现克唑替尼耐药后,一天使用两次艾乐替尼,87名患者的38%肿瘤缩

Alectinib versus Crizotinib in UntreatedALK-Positive Non–Small-Cell Lung Cancer

June 6, 2017DOI: 10.1056/NEJMoa1704795

Background

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non–small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease.

Methods

In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee–assessed progression-free survival, time to CNS progression, objective response rate, and overall survival.

Results

During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee–assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib).

Conclusions

As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann–La Roche; ALEX ClinicalTrials.gov number, NCT02075840.)

新英格兰医学杂志:ALEX 试验证实罗氏新药艾乐替尼治疗肺癌优于克唑替尼_印度特罗凯价钱

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