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非小细胞肺癌的靶向治疗:阿雷替尼

发表者:张品良 人已读

【非小细胞肺癌NCCN指南2017第7版】

Discussion 讨论

Treatment Approaches 治疗手段

Targeted Therapies 靶向治疗

Oral TKIs 口服的酪氨酸激酶抑制剂

Alectinib 阿雷替尼

Alectinib is an oral TKI ALK inhibitor that is approved by the FDA for patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib. The approval is based on two phase 2 trials showing overall response rates of 48% to 50% to alectinib in patients who had previously received crizotinib. In the larger trial by Ou et al, the control rate for CNS disease was 83% (95% CI, 74%–91%), and the median duration of response was 10.3 months (95% CI, 7.6–11.2 months). Of 84 patients with baseline CNS metastases, 23 (27%) had a complete CNS response. Of 23 patients with baseline CNS metastases and without previous brain RT, 10 (43%) had a complete CNS response to alectinib. Based on these trials and the FDA approval, the NCCN Panel recommends alectinib as subsequent therapy for patients with ALK-positive NSCLC who have progressed after crizotinib; patients who do not tolerate crizotinib may be switched to alectinib or ceritinib (if not previously given), or brigatinib. 山东第一医科大学附属肿瘤医院呼吸内科张品良

阿雷替尼是一种口服的TKI ALK抑制剂,已被FDA批准用于克唑替尼进展或不能耐受、ALK阳性的转移性非小细胞肺癌患者。批准是基于两项2期试验显示在既往接受过克唑替尼的患者中阿雷替尼的总有效率为48%-50%。在Ou等的更大试验中,CNS疾病的控制率为83%(95% CI,74%-91%),中位疗效持续时间是10.3个月(95% CI,7.6-11.2个月)。基线CNS转移的84例患者中,23例(27%)CNS完全缓解。23例基线CNS转移、既往未行脑RT的患者中,阿雷替尼治疗后10例(43%)CNS完全缓解。基于这些试验和FDA的批准,研究小组推荐阿雷替尼作为ALK阳性NSCLC患者在克唑替尼进展后的后续治疗;不耐受克唑替尼的患者可以转换至阿雷替尼或色瑞替尼(如果既往未给予)或布加替尼。

For the 2017 update (Version 7), the NCCN Panel now recommends alectinib as first-line therapy (category 1) for patients with ALK-positive metastatic NSCLC based on a recent phase 3 randomized trial (ALEX). Panel members also voted that alectinib is the preferred agent for first-line therapy for patients with metastatic NSCLC who are positive for ALK gene rearrangements. The phase 3 trial assessed first-line therapy with alectinib versus crizotinib in 303 patients with ALK-positive advanced NSCLC including those with asymptomatic CNS disease. Disease progression or death occurred in fewer patients receiving alectinib (41% [62/152]; median follow-up of 18.6 months) when compared with crizotinib (68% [102/151]; median follow-up of 17.6 months). The hazard ratio was 0.47 (95% CI, 0.34 to 0.65); P<.001) for disease progression or death. PFS was significantly increased with alectinib (68.4% [95% CI, 61.0 to 75.9] versus crizotinib (48.7% [95% CI, 40.4 to 56.9]. The median PFS was not reached for alectinib (95% CI, 17.7 months to not estimable) when compared with crizotinib at 11.1 months (95% CI, 9.1 to 13.1). Fewer patients receiving alectinib had CNS progression (12% [18/152] versus crizotinib (45% [68/151]). Response rates were 83% (126/152) in the alectinib group versus 75% (114/151) in the crizotinib group (P =.09). Patients receiving alectinib had fewer grade 3 to 5 adverse events when compared with crizotinib (41% [63/152] vs. 50% [75/151], respectively) even though patients received alectinib for longer duration than crizotinib (median, 17.9 vs. 10.7 months). There were also fewer deaths in the alectinib arm (3.3% [5/152]) versus the crizotinib arm (4.6% [7/151]); 2 treatment-related deaths were reported in the crizotinib arm and none in the alectinib arm. 

根据最近一项3期随机试验(ALEX),2017第7版更新,NCCN专家组目前推荐阿雷替尼(艾乐替尼)作为ALK阳性转移性非小细胞肺癌患者的一线治疗(1类)(见本讨论中的阿雷替尼)。专家组成员还投票决定阿雷替尼是ALK基因重排阳性的转移性非小细胞肺癌患者一线治疗首选药物。该3期试验评估了阿雷替尼对比克唑替尼一线治疗303例ALK阳性的晚期非小细胞肺癌,包括无症状的中枢神经系统病变患者。疾病进展或死亡的患者,与克唑替尼相比(68%[102/151];中位随访17.6个月),接受阿雷替尼的患者中较少(41%[62/152];中位随访18.6个月)。疾病进展或死亡风险比为0.47(95% CI,0.34-0.65;p<0.001)。与克唑替尼相比,阿雷替尼组的PFS显著延长(48.7[95% CI,40.4-56.9]对68.4[95% CI,61-75.9])。中位PFS,与克唑替尼在11.1个月内(95% CI,9.1-13.1)相比,阿雷替尼尚未达到(95% CI,17.7个月到不可估计)。中枢神经系统进展,与克唑替尼(45% [68/151])相比,接受阿雷替尼的患者更少(12%[18/152])。缓解率,阿雷替尼组为83%(126/152),而克唑替尼组为75%(114/151)(P = 0.09)。与接受克唑替尼的患者相比,接受阿雷替尼的患者有较少的3-5级不良事件(分别为50%[75/151]和41%[63/152]),尽管接受阿雷替尼的患者比接受克唑替尼的患者服药时间更长(平均17.9个月对10.7个月)。阿雷替尼组死亡更少(3.3%[5/152]),而克唑替尼组为(4.6% [7/151]);克唑替尼组报道2例治疗相关死亡,而阿雷替尼组没有一个。

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本文仅供健康科普使用,不能做为诊断、治疗的依据,请谨慎参阅

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发表于:2017-07-07 13:54

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