Tsakonas Georgios, Ekman Simon
Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
J Thorac Dis. 2018 May;10(Suppl 13):S1547-S1555. doi: 10.21037/jtd.2018.01.82.
A majority of non-small cell lung cancer (NSCLC), especially adenocarcinomas, harbour at least one oncogenic driver mutation that can potentially be a target for therapy. The treatment of these oncogene-addicted tumors has dramatically changed the outcome of these patients, where tyrosine kinase inhibitors (TKIs) of mutated epidermal growth factor receptor (EGFR) and rearranged anaplastic lymphoma kinase (ALK) have paved the way for a new era of precision cancer medicine. Another paradigm shift in the treatment of NSCLC, as well as numerous other tumor types, has been the introduction of immunotherapy (IO) with immune checkpoint inhibitors targeting mainly programmed cell death-1 (PD-1) or its ligand PDL-L1, where studies have demonstrated an increased survival versus standard treatment with chemotherapy, both in the first- and second-line setting. However, the role of IO in oncogene-addicted NSCLC is still unclear where most clinical data come from subgroup analyses with low number of patients in larger randomized trials, and these data do not support the use of IO after TKI in this category of NSCLC patients. The purpose of this review is to summarize the existing evidence about the use of IO in oncogenic-addicted NSCLC and highlight the issues that should be addressed in the future in order to define the role of IO for these patients.
大多数非小细胞肺癌(NSCLC),尤其是腺癌,至少存在一种致癌驱动基因突变,这些突变有可能成为治疗靶点。对这些致癌基因依赖型肿瘤的治疗极大地改变了患者的预后,其中,针对表皮生长因子受体(EGFR)突变和间变性淋巴瘤激酶(ALK)重排的酪氨酸激酶抑制剂(TKIs)为精准癌症医学的新时代铺平了道路。非小细胞肺癌以及许多其他肿瘤类型治疗中的另一个范式转变是引入了免疫疗法(IO),主要是使用靶向程序性细胞死亡蛋白1(PD-1)或其配体PD-L1的免疫检查点抑制剂,研究表明,在一线和二线治疗中,与标准化疗相比,免疫疗法可提高患者生存率。然而,免疫疗法在致癌基因依赖型非小细胞肺癌中的作用仍不明确,因为大多数临床数据来自大型随机试验中患者数量较少的亚组分析,且这些数据并不支持在这类非小细胞肺癌患者中TKI治疗后使用免疫疗法。本综述的目的是总结关于免疫疗法在致癌基因依赖型非小细胞肺癌中应用的现有证据,并强调未来为明确免疫疗法对这些患者的作用而应解决的问题。