Department of Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Cancer. 2024 Oct 1;130(19):3239-3250. doi: 10.1002/cncr.35423. Epub 2024 Jun 21.
The past year has offered significant advancements in the field of non-small cell lung cancer (NSCLC), both in the early and advanced disease settings. The identification of guideline-recommended actionable targets has provided the foundation for developing multiple new therapeutic agents. There has been a focus on developing drugs designed to overcome acquired resistance, a limitation of tyrosine kinase inhibitor-based therapy in lung cancer. In addition, there is an emerging trend toward combination therapies for patients in the first-line setting with the goal of preventing or delaying resistance. Another promising area of development has been the use of antibody-drug conjugates, where there are the initial reports of central nervous system efficacy and activity in patients with genomic alterations. Over the past year, numerous publications and presentations have highlighted multiple therapeutic advances, offering new treatment options for patients with NSCLC. The focus of this review is to summarize the most impactful findings, emphasizing their significance in the evolving treatment landscape for NSCLC. Several landmark trials in lung cancer with practice-changing clinical implications have been presented and published in 2023. This article reviews a selection of these trials as they relate to early and advanced-stage oncogene-driven lung cancer. The ADAURA and ALINA trials, in which targeted therapy given in the adjuvant setting has demonstrated improved clinical outcomes, are reviewed. In the advanced-stage setting, recent trials in the context of specific oncogene drivers are reviewed, including EGFR, ALK, ROS1, RET, ERBB2 (HER2), BRAF, MET exon 14 skipping (METex14), and KRAS alterations. Also discussed are the results of several trials that have evaluated the use of combination therapies and resistance-mechanism agnostic treatment strategies. PLAIN LANGUAGE SUMMARY: Targeted therapy plays an important role for patients with early and advanced-stage non-small cell lung cancer carrying specific genetic alterations. New strategies that combine multiple therapies are now being studied in randomized clinical trials, with the goal of enhancing the effectiveness of targeted therapy for patients with advanced lung cancer.
过去一年，非小细胞肺癌（NSCLC）的早期和晚期疾病领域都取得了显著进展。确定了指南推荐的可操作靶点，为开发多种新的治疗药物奠定了基础。重点是开发旨在克服获得性耐药的药物，这是肺癌酪氨酸激酶抑制剂治疗的一个局限性。此外，对于一线治疗的患者，出现了联合治疗的趋势，目的是预防或延迟耐药。另一个有发展前景的领域是使用抗体药物偶联物，有初步报告称这些药物对具有基因组改变的患者具有中枢神经系统疗效和活性。在过去的一年中，大量出版物和演讲强调了多种治疗进展，为 NSCLC 患者提供了新的治疗选择。本综述的重点是总结最有影响力的发现，强调它们在 NSCLC 不断发展的治疗格局中的意义。2023 年提出并发表了多项具有改变实践临床意义的肺癌标志性试验。本文回顾了其中一些与驱动基因的早期和晚期 NSCLC 相关的试验。回顾了在辅助治疗中使用靶向治疗可改善临床结果的 ADAURA 和 ALINA 试验。在晚期疾病中，还回顾了特定驱动基因背景下的最新试验，包括 EGFR、ALK、ROS1、RET、ERBB2（HER2）、BRAF、MET 外显子 14 跳跃（METex14）和 KRAS 改变。还讨论了几项试验的结果，这些试验评估了联合治疗和耐药机制不可知的治疗策略的应用。
