The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes for patients with resectedEGFR- andALK-positive NSCLC, respectively, changing the standard of care in these subgroups. More recently, the LAURA trial showed the efficacy of osimertinib after chemoradiotherapy in patients with unresectable stage III NSCLC harboringEGFRmutations. Numerous trials are still ongoing to investigate neoadjuvant/perioperative TKIs in several oncogene-driven NSCLC. In addition, several ICBs have been tested and approved as adjuvant (atezolizumab and pembrolizumab), neoadjuvant (nivolumab), and perioperative treatments (pembrolizumab) for patients with resectable early-stage NSCLC. Despite these advances, many challenges remain regarding the use of TKIs and ICBs in this setting, including the optimal duration of adjuvant TKI or induction ICB therapy, the role of minimal residual disease to identify patients at high-risk of disease relapse and to guide adjuvant treatment decisions, and the role of adjuvant chemotherapy in resected oncogene-driven NSCLC. Furthermore, potential predictive biomarkers for efficacy are needed to eventually intensify the entire perioperative strategies. This review aims to summarize and discuss the available evidence, the ongoing trials, and the challenges associated with TKI- and ICB-based approaches in early-stage NSCLC.
近期，酪氨酸激酶抑制剂（TKIs）和免疫检查点阻断剂（ICBs）在早期非小细胞肺癌（NSCLC）治疗中的应用，通过显著改善患者预后，极大地改变了治疗策略。奥希替尼和阿来替尼作为TKIs，分别在切除后的EGFR阳性和ALK阳性NSCLC患者中显示出显著的疗效提升，从而改变了这些亚组的治疗标准。最近，LAURA试验证明了奥希替尼在放化疗后对携带EGFR突变的不可切除III期NSCLC患者的有效性。目前仍有大量试验正在研究新辅助/围手术期TKIs在多种致癌基因驱动的NSCLC中的应用。此外，多种ICBs已作为辅助治疗（阿特珠单抗和帕博利珠单抗）、新辅助治疗（纳武利尤单抗）和围手术期治疗（帕博利珠单抗）在可切除的早期NSCLC患者中得到测试和批准。尽管取得了这些进展，但TKIs和ICBs在此背景下的应用仍面临诸多挑战，包括辅助TKI或诱导ICB治疗的最佳持续时间、微小残留病灶在识别高复发风险患者和指导辅助治疗决策中的作用，以及辅助化疗在切除的致癌基因驱动NSCLC中的角色。此外，需要寻找潜在的疗效预测生物标志物，以最终优化整个围手术期治疗策略。本综述旨在总结和讨论现有证据、正在进行的试验，以及与基于TKI和ICB的早期NSCLC治疗方法相关的挑战。
肿瘤(癌症)患者之家