Medical Oncology Department, Centro Integral Oncología Clara Campal Barcelona-HM Delfos, Barcelona, Spain.
Section of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
J Thorac Oncol. 2019 Jul;14(7):1134-1155. doi: 10.1016/j.jtho.2019.03.022. Epub 2019 Apr 16.
In 2018 research in the field of advanced NSCLCs led to an expanded reach and impact of immune checkpoint inhibitors (ICIs) as part of a frontline treatment strategy, regardless of histologic subtype, with ICI use extended to include stage III disease, shifting the prognosis of all these patients. This new standard first-line approach opens a gap in standard second-line treatment, and older combinations may again become standard of care after progression during treatment with an ICI. The characterization of predictive biomarkers, patient selection, the definition of strategies with ICI combinations upon progression during treatment with ICIs, as well as prospective evaluation of the efficacy of ICIs in subpopulations (such as patients with poor performance status or brain metastases) represent upcoming challenges in advanced thoracic malignancies. In oncogene-addicted NSCLC three major steps were taken during 2018: next-generation tyrosine kinase inhibitors have overtaken more established agents as the new standard of care in EGFR and ALK receptor tyrosine kinase gene (ALK)-positive tumors. Mechanisms of acquired resistance have been reported among patients treated with next-generation EGFR tyrosine kinase inhibitors, reflecting the diversity of the landscape. One major step forward was the approval of personalized treatment in very uncommon genomic alterations, mainly fusions. This raises a new question about the challenge of implementation of next-generation sequencing in daily clinical practice to detect new and uncommon genomic alterations and to capture the heterogeneity of the mechanisms of acquired resistance during treatment, as well as the need to extend research into new therapeutic strategies to overcome them.
在 2018 年，先进 NSCLC 领域的研究导致免疫检查点抑制剂 (ICI) 的应用范围扩大，并产生了更大的影响，成为一线治疗策略的一部分，无论组织学亚型如何，ICI 的应用范围扩大到包括 III 期疾病，从而改变了所有这些患者的预后。这种新的标准一线治疗方法在标准二线治疗中留下了空白，在接受 ICI 治疗期间进展后，旧的联合治疗方案可能再次成为标准治疗方案。预测生物标志物的特征、患者选择、ICI 联合治疗进展后的策略定义，以及在亚人群（如体能状态差或脑转移患者）中评估 ICI 的疗效，都是晚期胸部恶性肿瘤未来面临的挑战。在致癌基因依赖型 NSCLC 中，2018 年取得了三项重大进展：下一代酪氨酸激酶抑制剂已经超越了更成熟的药物，成为 EGFR 和 ALK 受体酪氨酸激酶基因 (ALK) 阳性肿瘤的新标准。在接受下一代 EGFR 酪氨酸激酶抑制剂治疗的患者中，已经报道了获得性耐药的机制，反映了这种情况的多样性。向前迈出的一大步是批准对非常罕见的基因组改变（主要是融合）进行个体化治疗。这就提出了一个新的问题，即在日常临床实践中实施下一代测序以检测新的和罕见的基因组改变，以及在治疗期间捕获获得性耐药机制的异质性，并需要扩展研究以克服这些机制的新治疗策略。
