First-line systemic therapy for patients with advanced or metastatic non-small cell lung cancer (NSCLC) has rapidly evolved over the past two decades. First, molecularly targeted therapy for a growing number ofgain-of-functionmolecular targets has been shown to improve progression-free survival (PFS) and overall survival (OS) with favorable toxicity profiles compared to platinum-containing chemotherapy and can be given as first-line systemic therapy in ~25% of patients with NSCLC. Actionable genetic alterations include EGFR, BRAF V600E, and MET exon 14 splicing site-sensitizing mutations, as well as ALK-, ROS1-, RET-, and NTRK-gene fusions. Secondly, inhibitors of programmed cell death protein 1 or its ligand 1 (PD-1/L1) such as pembrolizumab, atezolizumab, or cemiplimab monotherapy have become a standard of care for ~25% of patients with NSCLC whose tumors have high PD-L1 expression (total proportion score (TPS) ≥50%) and no sensitizing EGFR/ALK alterations. Lastly, for the remaining ~50% of patients who are fit and whose tumors have no or low PD-L1 expression (TPS of 0–49%) and no sensitizing EGFR/ALK aberrations, platinum-containing chemotherapy with the addition of a PD-1/L1 inhibitor alone or in combination of a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor improves PFS and OS compared to chemotherapy alone. The objectives of this review are to summarize the current data and perspectives on first-line systemic treatment in patients with unresectable NSCLC and propose a practical algorithm for implementing precision biomarker testing at diagnosis.
晚期或转移性非小细胞肺癌（NSCLC）患者的一线系统治疗在过去二十年中迅速发展。首先，针对日益增多的功能获得性分子靶点的靶向治疗已被证实，相较于含铂化疗，能够改善无进展生存期（PFS）和总生存期（OS），且具有更优的毒性特征，可作为约25% NSCLC患者的一线系统治疗。可靶向的基因改变包括EGFR、BRAF V600E和MET外显子14剪接位点敏感突变，以及ALK、ROS1、RET和NTRK基因融合。其次，程序性细胞死亡蛋白1或其配体1（PD-1/L1）抑制剂，如帕博利珠单抗、阿替利珠单抗或西米普利单抗单药治疗，已成为约25%肿瘤具有高PD-L1表达（总比例评分（TPS）≥50%）且无EGFR/ALK敏感突变的NSCLC患者的标准治疗。最后，对于其余约50%体能状况良好、肿瘤无或低PD-L1表达（TPS为0–49%）且无EGFR/ALK敏感突变的患者，在含铂化疗基础上联合PD-1/L1抑制剂单用或联合细胞毒性T淋巴细胞相关蛋白4（CTLA-4）抑制剂，相较于单纯化疗，可改善PFS和OS。本综述旨在总结当前关于不可切除NSCLC患者一线系统治疗的数据与观点，并提出在诊断时实施精准生物标志物检测的实用流程。
肿瘤(癌症)患者之家