过去二十年来，晚期或转移性非小细胞肺癌 (NSCLC) 患者的一线全身治疗迅速发展。首先，针对越来越多的功能获得性分子靶标的分子靶向治疗已被证明可以改善无进展生存期 (PFS) 和总生存期 (OS)，与含铂化疗相比，具有良好的毒性特征，并且可以作为约 25% 的 NSCLC 患者的一线全身治疗。可操作的基因改变包括 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，例如派姆单抗、阿替利珠单抗或西米普利单抗单药疗法，已成为约 25% 肿瘤具有高 PD-L1 的 NSCLC 患者的标准治疗表达（总比例评分（TPS）≥50%）并且没有致敏 EGFR/ALK 改变。最后，对于剩余约 50% 的健康患者，其肿瘤没有或低 PD-L1 表达（TPS 为 0-49%）且没有致敏 EGFR/ALK 畸变，可在含铂化疗的基础上添加 PD与单独化疗相比，单独使用 -1/L1 抑制剂或与细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA-4) 抑制剂联合使用可改善 PFS 和 OS。本综述的目的是总结不可切除的 NSCLC 患者一线系统治疗的当前数据和观点，并提出一种在诊断时实施精准生物标志物测试的实用算法。

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 of gain-of-function molecular 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.