CSCO 2018:NSCLC脑转移真实世界治疗的讨论

2018-09-23 阿拉蕾 中国医学论坛报

肺癌是我国最常见的恶性肿瘤之一,非小细胞肺癌(NSCLC)是肺癌中最常见的类型,约占85%。肺癌最常见的远处转移部位之一是脑部,出现脑转移的肺癌患者预后差,自然平均生存时间仅1至2个月。

肺癌是我国最常见的恶性肿瘤之一,非小细胞肺癌NSCLC)是肺癌中最常见的类型,约占85%。肺癌最常见的远处转移部位之一是脑部,出现脑转移的肺癌患者预后差,自然平均生存时间仅1至2个月。

随着放射治疗技术的进步和分子靶向治疗等新疗法的迅速发展,为晚期肺癌脑转移提供了更多的治疗手段和更多的期待。

2018年9月19日至9月23日,第二十一届全国临床肿瘤学大会暨2018年中国临床肿瘤学会(CSCO)学术年会在厦门召开。

会议期间,上海市肺科医院苏春霞教授、中国医学科学院肿瘤医院段建春教授和湖南省肿瘤医院杨农教授做客中国医学论坛报社CSCO官方直播间,围绕NSCLC脑转移的治疗展开精彩讨论,本文就重点内容作整理。

肺癌脑转移的治疗现状

随着化疗、靶向治疗和免疫治疗的不断进步,使得肺癌患者的生存期显著延长,同时脑转移发生率也逐步提高。由于大部分药物无法通过血脑屏障,因此肺癌脑转移患者的预后非常差,如果这部分患者不能得到及时、有效的治疗,自然病程只有2个月左右。

近年来,靶向药物的快速发展为这部分患者带来希望。BRAIN研究结果显示,针对脑转移病灶≥3个、至少有一个直径>1 cm、伴有EGFR突变的患者,使用埃克替尼治疗能显著改善NSCLC脑转移患者的无进展生存期(PFS)和总生存期(OS)。

相较一、二代EGFR-TKI,三代EGFR-TKI奥希替尼能有效通过血脑屏障,脑积液中浓度理想。AURA系列研究结果显示,EGFR突变合并T790M突变的NSCLC脑转移患者,接受奥希替尼治疗后脑转移进展风险显著降低,能有效控制患者的病情进展。

BRAIN研究结果显示,相比全脑放射治疗,靶向药物治疗能取得更理想的生存获益,增强了我们临床应用靶向药物的信心。无论基线时即有脑转移,还是后续出现脑转移的患者,AZD9291(即奥希替尼)在整个AURA系列研究中均表现优异。

随着EGFR-TKI类药物的应用增加,肺癌的中位生存期已经接近5年,可以把它看作为“慢性疾病”,肺癌的全程管理也成为了热议话题。

新版CSCO NSCLC指南解读

今年新版CSCO NSCLC诊疗指南中指出,针对EGFR突变、脑转移灶≥3个的患者,推荐使用EGFR-TKI治疗(证据等级:1B)。在实际临床工作中,我们需要根据患者的实际情况,个体化制定治疗策略,包括是否有临床症状、是否存在合并症以及脑转移灶大小等。

针对无症状或症状轻微,且脑转移灶部位不属于重要功能区的患者,可以考虑首选EGFR-TKI治疗,而把全脑放射治疗这种对脑组织有损伤的治疗策略适当后移。

既往研究显示,无论是EGFR-TKI还是ALK-TKI类药物,血脑屏障通透性均较为理想,无论对脑转移灶还是其他部位肿瘤的压迫症状,使用此类药物后均能出现明显的缓解。

因此,无论病灶数量,都能尝试给予患者EGFR-TKI治疗。如果患者对EGFR-TKI类药物敏感,病情可能在短期内改善,此后再进行化疗或放疗,或许能适当降低治疗剂量从而使患者获益。

实际临床工作中许多专家已经形成共识,针对脑转移灶负荷较大的患者,会考虑一线选用奥希替尼治疗。FLAURA研究显示,与一代EGFR-TKI药物相比,奥希替尼在生存获益方面具有一定优势。奥希替尼不仅针对EGFR-T790M突变,且具有更理想的血脑屏障通透能力。

放疗和靶向治疗,孰先孰后?

目前全程化管理已经使肺癌患者、尤其是晚期伴脑转移患者的生存期得到极大的延长。靶向和免疫治疗已经逐渐走入我们的视野,但是放射治疗仍旧是NSCLC脑转移的重要治疗方法。如何定位放疗的地位,如何对各种治疗方法进行“排兵布阵”,尚有争议。

全脑放射治疗会造成脑组织损伤,且具有累积效应,因此制定放疗策略时需慎重。如果我们能把放疗和分子靶向药物有效结合,将会使患者获益。还是回到之前强调的问题,我们需要根据患者的实际情况制定个体化治疗方案,包括转移灶的数量、位置、大小、临床症状等。

针对NSCLC脑转移的患者,该如何应对?内科医生与放疗科医生具有各自的观点。除了之前提到的临床症状、转移灶位置、肿瘤负荷等,是否存在EGFR敏感突变也是制定治疗策略时非常重要的考虑因素。放疗和靶向药物治疗,我们到底应该优先选择哪一个?

目前的循证学依据均是回顾性研究,尚缺乏较大规模的随机、对照、前瞻性临床研究,非常期待有相关证据能够出现为我们解答这个问题。

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CLIN CANCER RES:Abemaciclib增强非小细胞肺癌放疗敏感性

CLIN CANCER RES近期发表了一篇文章,研究CDK4/6抑制剂Abemaciclib增强非小细胞肺癌细胞放疗敏感性的机制。

JCO:Capmatinib联合Gefitinib治疗EGFR抑制失败的非小细胞肺癌患者

EGFR-TKI治疗失败后,约26%的非小细胞肺癌患者会出现上皮间质转化(MET)异常。Capmatinib是一种选择性MET抑制剂,在获得性EGFR突变、EGFR-TKI类药物耐药的模型中Capmatinib联合Gefitinib具有活性。JCO近期发表了一篇文章,研究Capmatinib联合Gefitinib治疗EGFR突变,MET异常且接受EGFR-TKI治疗后出现疾病进展的非小细胞肺癌患者