PDF(Pubmed)
Abstract：
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.
摘要：
在过去的20年里,非小细胞肺癌（NSCLC）患者的护理模式发生了转变，他们现在有一系列的全身治疗选择，包括靶向治疗，化疗,免疫疗法（ICI），和抗体-药物缀合物(ADC)。这些癌症中的一部分在致癌基因中具有单个可识别的改变，这些改变驱动其增殖和癌症进展，被称为“癌基因成瘾”。这些“驱动改变”在大约三分之二的肺腺癌患者中被发现，通过下一代测序或其他正交试验。在ICI的早期临床开发中注意到，癌基因成瘾的NSCLC患者可能对ICI有不同的反应。当使用ICIs治疗时，癌基因成瘾的NSCLC患者的毒性信号似乎也有所不同，具体取决于存在的改变和使用的特定靶向药物。对这些临床观察的根本原因有更深入的了解已成为NSCLC研究的重要领域。在这次审查中,我们根据特定突变分析ICI的有效性和安全性，并考虑未来可能的方向，以减轻癌基因成瘾的NSCLC患者的安全性问题并改善预后。
