Qian Fangfei, Zhong Runbo, Zhong Hua
Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Transl Lung Cancer Res. 2025 Jul 31;14(7):2853-2868. doi: 10.21037/tlcr-2025-684. Epub 2025 Jul 28.
Although immunotherapy has become the standard treatment for driver gene-negative advanced non-small cell lung cancer (NSCLC), its efficacy in driver gene-positive NSCLC patients remains conversational. This narrative review systematically and critically analyzes recently published literature, aiming to improve the current landscape of immunotherapy for driver gene-positive NSCLC.
The databases of PubMed, Web of Science, Scopus, and Google Scholar were searched for relevant articles, including those published in leading journals and conference proceedings. Search queries were constructed using keywords ("immunotherapy", "non-small cell lung cancer", "driver gene-positive") and their combinations. Literature was included via dual independent screening and team meetings, followed by comprehensive interpretation, resulting in a high-quality literature corpus focused on advances in immunotherapy for driver gene-positive NSCLC.
This article reviews the recent advances and challenges in immunotherapy for driver gene-positive NSCLC, focusing on common driver gene mutations. Significant variations exist in how different driver genes regulate the tumor immune microenvironment, leading to disparate immunotherapy response rates. While targeted therapy is the first-line treatment for NSCLC with epidermal growth factor receptor () mutations, immunotherapy combinations should be explored when drug resistance occurs. Immunotherapy plus chemotherapy is preferred in patients with Kirsten rat sarcoma viral oncogene homolog ()-mutated NSCLC, whereas antibody-drug conjugates plus immunotherapy may be more appropriate for NSCLC with human epidermal growth factor receptor 2 () alterations. Despite the accumulation of studies of patients with common alterations, studies of patients with uncommon alterations are still lacking. Neoadjuvant immunotherapy combined with chemotherapy is currently being explored for driver gene-positive NSCLC.
Many questions remain about the use of immunotherapy for the treatment of driver gene-positive NSCLC. With optimized biomarker and combination therapies, individualized strategies may be further developed for overcoming drug resistance.
尽管免疫疗法已成为驱动基因阴性的晚期非小细胞肺癌（NSCLC）的标准治疗方法，但其在驱动基因阳性的NSCLC患者中的疗效仍存在争议。本叙述性综述系统且批判性地分析了最近发表的文献，旨在改善驱动基因阳性NSCLC的免疫治疗现状。
检索了PubMed、Web of Science、Scopus和谷歌学术数据库中的相关文章，包括发表在主要期刊和会议论文集上的文章。使用关键词（“免疫疗法”、“非小细胞肺癌”、“驱动基因阳性”）及其组合构建检索式。通过双人独立筛选和团队会议纳入文献，随后进行全面解读，从而形成了一个聚焦于驱动基因阳性NSCLC免疫治疗进展的高质量文献库。
本文回顾了驱动基因阳性NSCLC免疫治疗的最新进展和挑战，重点关注常见的驱动基因突变。不同的驱动基因调节肿瘤免疫微环境的方式存在显著差异，导致免疫治疗反应率各不相同。虽然靶向治疗是表皮生长因子受体（EGFR）突变的NSCLC的一线治疗方法，但当出现耐药时应探索免疫治疗联合方案。在 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）突变的NSCLC患者中，免疫治疗联合化疗是首选，而抗体药物偶联物联合免疫治疗可能更适合于人表皮生长因子受体2（HER2）改变的NSCLC。尽管对常见改变患者的研究有所积累，但对罕见改变患者的研究仍然缺乏。目前正在探索新辅助免疫治疗联合化疗用于驱动基因阳性的NSCLC。
关于免疫疗法用于治疗驱动基因阳性NSCLC仍存在许多问题。通过优化生物标志物和联合疗法，可能会进一步制定个性化策略来克服耐药性。
