Princess Margaret Cancer Centre, Division of Medical Oncology, University of Toronto, 7W389 700 University Avenue, Toronto, ON, M5G 1Z5, Canada.
Princess Margaret Cancer Centre, Division of Medical Oncology, University of Toronto, 7-913 700 University Avenue, Toronto, ON, M5G 1Z5, Canada.
Curr Treat Options Oncol. 2019 Feb 18;20(3):21. doi: 10.1007/s11864-019-0617-6.
The treatment of advanced non-small cell lung cancer (NSCLC) has evolved to include targeted therapy, immunotherapy as well as chemotherapy for selected patients in the first-line setting. Angiogenesis inhibitors have been used in combination with chemotherapy in the first-line and maintenance settings providing improved progression-free survival (PFS) and objective response rate (ORR), as well as overall survival (OS) in selected studies. Biologic rationale exists for combining anti-angiogenic agents with immunotherapy and targeted kinase inhibitors (TKIs). A recent study has demonstrated improved survival when anti-PD-L1 therapy was added to chemotherapy plus bevacizumab. Subgroup analysis of patients with mutations in the epidermal growth factor receptor (EGFR) gene and rearrangements in the anaplastic lymphoma kinase (ALK) gene also demonstrated benefit with combined anti-PD-L1, bevacizumab, and platinum chemotherapy. Further investigation into combination therapy is warranted in the EGFR- and ALK-positive population given this signal. Anti-angiogenics combined with EGFR-targeted treatment in the wild-type population have shown modest PFS benefit with no OS benefit, and their routine use has not been adopted. The combination of EGFR inhibitors plus vascular endothelial growth factor (VEGF) inhibitors in the EGFR mutation-positive population has demonstrated substantial improvements in response and PFS; however, given the higher toxicity and lack of survival benefit to date, combination therapy in this group should be used with caution. At the present time, use of bevacizumab can be recommended with atezolizumab and chemotherapy for the first-line treatment of non-squamous NSCLC patients. Data with other checkpoint inhibitors and anti-angiogenics are too early to make firm recommendations regarding their use.
治疗晚期非小细胞肺癌（NSCLC）已发展到包括针对特定患者的一线治疗靶向治疗、免疫治疗以及化疗。血管生成抑制剂已与化疗联合应用于一线和维持治疗，在某些研究中改善了无进展生存期（PFS）和客观缓解率（ORR），以及总生存期（OS）。将抗血管生成药物与免疫治疗和靶向激酶抑制剂（TKI）联合使用具有生物学依据。最近的一项研究表明，在化疗加贝伐珠单抗的基础上联合使用抗 PD-L1 治疗可提高生存率。表皮生长因子受体（EGFR）基因突变和间变性淋巴瘤激酶（ALK）基因重排患者的亚组分析也表明，联合抗 PD-L1、贝伐珠单抗和铂类化疗具有获益。鉴于这一信号，在 EGFR 和 ALK 阳性人群中进一步研究联合治疗是合理的。抗血管生成药物联合 EGFR 靶向治疗在野生型人群中显示出适度的 PFS 获益，但没有 OS 获益，因此尚未常规采用。在 EGFR 突变阳性人群中，EGFR 抑制剂加血管内皮生长因子（VEGF）抑制剂的联合治疗显著改善了反应和 PFS；然而，鉴于目前更高的毒性和缺乏生存获益，该组的联合治疗应谨慎使用。目前，贝伐珠单抗联合阿特珠单抗和化疗可用于一线治疗非鳞状 NSCLC 患者。其他检查点抑制剂和抗血管生成药物的数据还为时过早，无法就其使用做出明确的推荐。
