于壮教授:精准治疗“慢病”管理ALK阳性非小细胞肺癌

2019-07-18 佚名 ioncology

EGFR和ALK等驱动基因的发现不仅使非小细胞肺癌(NSCLC)的治疗实现了分型变革,也促进单一治疗模式的改变。目前,非小细胞肺癌的治疗已经进入精准分层治疗时代,靶向治疗是分层诊疗最典型最有价值的体现。

EGFR和ALK等驱动基因的发现不仅使非小细胞肺癌NSCLC)的治疗实现了分型变革,也促进单一治疗模式的改变。目前,非小细胞肺癌的治疗已经进入精准分层治疗时代,靶向治疗是分层诊疗最典型更有价值的体现。

NSCLC精准治疗的现状和前景

目前非小细胞肺癌的治疗进展非常快,已经真正进入精准治疗时代。我国的肺癌发病率位居所有癌症的第一位,死亡率也是第一位。无论是临床医生还是基础科学家对此均非常重视。随着国民生活水平的提高,在高危人群,比如45岁以上的重度吸烟者当中,体检逐渐普及。随着肺癌筛查的普及和病人早期发现的增加,有许多早期肺癌病人可以通过胸外科手术得以根治。但流行病学调查数据显示,仍有70%-75%的病人一经发现即是晚期肺癌。对这部分病人而言,十多年前的治疗是以化疗为主,但从2000年开始,IPASS试验宣告了靶向时代的到来。随着后面各种靶点的不断发现,各种靶向药物的不断研发,肺癌的治疗真正进入了精准治疗时代。

非小细胞肺癌靶向治疗的研究热点以及未来靶向治疗发展路线

目前我们对肺癌细胞基因突变的认识不断加深。随着检测技术的不断提高,学者们发现了越来越多的突变基因靶点,不断开发新的靶向药物。晚期肺癌,尤其是肺腺癌的病人,有约40%为EGFR突变阳性,除此之外,有5%-7%的ALK突变阳性,以及约1%的ROS-1以及更少数的C-MET等。既往仅推荐对晚期肺癌病人作EGFR检测,但现在我们逐渐认识到,应当做一个整体的基因突变检测,不能放弃任何一个基因突变位点。基因突变的病人对靶向治疗更敏感,可通过靶向治疗获得更长的生存时间。通过一代、二代ALK抑制剂治疗的全程管理,病人的生存时间甚至能超过90个月。这是非常了不起的。

ALK阳性的非小细胞肺癌是否将全面进入慢病时代?

在二代ALK抑制剂没有上市时,一线使用克唑替尼治疗后,若疾病进展,可选用的二线治疗方案只有化疗,病人的生活质量、疾病稳定时间及总生存时间均无法令人满意。随着塞瑞替尼等一系列新的ALK抑制剂上市,我们的可选药物更多。可以一线选择塞瑞替尼,使病人的稳定时间更长。若一线选择克唑替尼治疗后,病人出现进展,尤其是针对脑转移的病人,二线选择塞瑞替尼,疾病稳定时间比选用化疗更长。前面提到法国的研究数据显示,病人通过一线、二线靶向药物的治疗,生存时间可达到将近90个月。这对于晚期癌症病人,可以实现真正进入慢病管理的时代了。

ALK抑制剂联合用药的进展以及进一步优化全程管理

肿瘤细胞的特性有血管增殖、凋亡抑制、免疫逃逸等,这意味着肿瘤的治疗应该是整体的、多角度的联合用药。对ALK基因突变阳性的病人,如何通过塞瑞替尼靶向药物的合理应用,能让病人在取得满意疗效的同时,生活质量更高,无病生存的维持时间更长,我认为可以从联合治疗的角度来进行探索,比如塞瑞替尼靶向治疗的基础上联合抗血管生成药物,联合免疫治疗,以及耐药以后如何联合化疗,都是今后探索的方向。我相信随着用药经验的增加,治疗全程管理经验的丰富,后续的多角度多途径的治疗方案会日趋成熟。

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    2019-12-01 xjy02
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