刘基巍教授:精准时代下ALK阳性NSCLC的治疗新选择

2019-07-23 佚名 ioncology

精准治疗时代下,驱动基因阳性非小细胞肺癌(NSCLC)的治疗进展日新月异。

精准治疗时代下,驱动基因阳性非小细胞肺癌NSCLC)的治疗进展日新月异。

精准医疗时代:NSCLC治疗新选择

2018年,我国17种抗癌新药纳入医保报销目录,不仅为肿瘤治疗提供了新的药物选择,也极大程度减轻了我国肿瘤患者的用药负担。非小细胞肺癌作为引领精准医疗的瘤种之一,基因检测至关重要,EGFR、ALK、ROS1等常见基因的检测已列入国内外治疗指南。在常见的NSCLC突变基因中,EGFR突变已被大家所熟知,EGFR抑制剂也已发展到第三代。对于第2大常见突变基因,ALK融合突变阳性患者的靶向治疗效果也相当好,这一突变甚至被称为“黄金突变”。目前ALK抑制剂研发进展飞速,继第一代克唑替尼之后,出现了第二代ALK抑制剂塞瑞替尼、阿来替尼,特别是塞瑞替尼已纳入医保,治疗可及性大大提高,切实地令患者获得生存获益。

二代vs一代ALK抑制剂:实力胜出

以进入医保的二代ALK抑制剂塞瑞替尼为例,较一代药物的优势在于:(1)可以通透血脑屏障,对脑转移患者有效;(2)ALK通路抑制能力强于一代,塞瑞替尼的抑制能力是克唑替尼的20倍。因此,二代药物无疑是一代克唑替尼耐药后的最佳选择。目前,塞瑞替尼也已被批准用于治疗克唑替尼耐药或不耐受的ALK阳性NSCLC。

ALK阳性NSCLC一线之争:群雄逐鹿

ALK抑制剂经历了从一代到二代的研发,三代将来也可能进入中国。对于ALK阳性NSCLC, 一线治疗选择众多,美国NCCN指南将一代克唑替尼、二代塞瑞替尼和阿来替尼都列入了一线选择。二代药物塞瑞替尼一线应用依据基于ASCEND-4临床试验,塞瑞替尼一线对比化疗,PFS显着提高(16.6 vs.8.1月)。因此,一线或可直接选择二代塞瑞替尼进行治疗。尤其需要注意的是,塞瑞替尼可通过血脑屏障,因此对于有脑转移的ALK阳性NSCLC患者疗效非常好。临床试验中,塞瑞替尼治疗脑转移的有效率可达70%,而化疗仅为30%。

关于塞瑞替尼的应用剂量,国际标准的塞瑞替尼剂量是750mg/天。针对亚裔人群,ASCEND-8临床实验中设计了450mg随餐一组,结果显示750mg空腹和450mg随餐组的客观缓解率和疾病控制率相当,450mg随餐组肠道耐受性明显改善,450mg随餐组一线治疗的PFS已经超过25个月,而塞瑞替尼750mg一线治疗的PFS为16个月。因此,对亚裔患者,塞瑞替尼的剂量提议使用450mg随餐口服,以期为患者带来更大临床获益。

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    2020-02-10 xjy02
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    2020-07-02 gujh
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    2019-07-23 肿肿

    NSCLC下一步突破在于新靶点了,靶向治疗和免疫治疗基本见顶了,再有新的就需要新机制了

    0

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