Lavaud Pernelle, Bortolot Martina, Zullo Lodovica, O'Reilly David, Naidoo Jarushka, Mountzios Giannis, Mercier Olaf, Hendriks Lizza E L, Remon Jordi
Gustave Roussy, Department of Cancer Medicine, Paris-Saclay University, 114, rue Edouard Vaillant, 94805 Villejuif, France.
Department of Respiratory Medicine, Maastricht University Medical Centre, GROW School for Oncology and Reproduction, 6229 ER Maastricht, The Netherlands.
Cancers (Basel). 2024 Aug 6;16(16):2779. doi: 10.3390/cancers16162779.
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 resected - and -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 harboring mutations. 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.
酪氨酸激酶抑制剂（TKIs）和免疫检查点阻滞剂（ICBs）近期在早期非小细胞肺癌（NSCLC）治疗中的出现，通过改善该情况下的预后显著改变了治疗策略。奥希替尼和阿来替尼这两种TKIs，分别在切除术后且 阳性的NSCLC患者中显示出显著的疗效改善，改变了这些亚组的治疗标准。最近，LAURA试验显示了奥希替尼在含 突变的不可切除III期NSCLC患者放化疗后的疗效。仍有许多试验正在进行，以研究几种致癌基因驱动的NSCLC中的新辅助/围手术期TKIs。此外，几种ICBs已被测试并批准用于可切除的早期NSCLC患者的辅助治疗（阿替利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）。尽管取得了这些进展，但在这种情况下使用TKIs和ICBs仍存在许多挑战，包括辅助TKI或诱导ICB治疗的最佳持续时间、微小残留病在识别疾病复发高危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的NSCLC中的作用。此外，最终加强整个围手术期策略需要潜在的疗效预测生物标志物。本综述旨在总结和讨论早期NSCLC中基于TKI和ICB方法的现有证据、正在进行的试验以及相关挑战。
