Over the past 20 years, there has been a paradigm shift in the care of patients with non-small cell lung cancer (NSCLC), who now have a range of systemic treatment options including targeted therapy, chemotherapy, immunotherapy (ICI), and antibody–drug conjugates (ADCs). A proportion of these cancers have single identifiable alterations in oncogenes that drive their proliferation and cancer progression, known as “oncogene-addiction”. These “driver alterations” are identified in approximately two thirds of patients with lung adenocarcinomas, via next generation sequencing or other orthogonal tests. It was noted in the early clinical development of ICIs that patients with oncogene-addicted NSCLC may have differential responses to ICI. The toxicity signal for patients with oncogene-addicted NSCLC when treated with ICIs also seemed to differ depending on the alteration present and the specific targeted agent used. Developing a greater understanding of the underlying reasons for these clinical observations has become an important area of research in NSCLC. In this review, we analyze the efficacy and safety of ICI according to specific mutations, and consider possible future directions to mitigate safety concerns and improve the outcomes for patients with oncogene-addicted NSCLC.
过去20年间，非小细胞肺癌（NSCLC）患者的诊疗模式发生了范式转变，目前已有包括靶向治疗、化疗、免疫检查点抑制剂（ICI）及抗体偶联药物（ADC）在内的多种全身治疗方案可供选择。其中部分肺癌存在驱动肿瘤增殖与进展的单一可识别致癌基因变异，即"致癌基因成瘾"现象。通过新一代测序或其他正交检测技术，约三分之二的肺腺癌患者可检测到这类"驱动基因变异"。在ICI早期临床研发阶段即发现，致癌基因成瘾型NSCLC患者对ICI的应答存在差异。此类患者接受ICI治疗时的毒性特征亦因基因变异类型及所用靶向药物的不同而呈现差异。深入探究这些临床现象背后的机制，已成为NSCLC研究的重要领域。本综述通过分析特定基因突变背景下ICI的疗效与安全性，探讨未来可能的研究方向，以期降低治疗风险并改善致癌基因成瘾型NSCLC患者的临床结局。
肿瘤(癌症)患者之家