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Abstract：
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.
摘要：
在过去的二十年中，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,与含铂化疗相比，用于越来越多的功能获得分子靶标的分子靶向治疗已被证明可改善无进展生存期（PFS）和总生存期（OS），并具有良好的毒性，并且可作为一线给予约25％的NSCLC患者的全身治疗。可行的遗传改变包括EGFR，BRAFV600E,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）的抑制剂，如pembrolizumab，阿替珠单抗,或cemiplimab单药治疗已成为约25%的NSCLC患者的治疗标准,这些患者的肿瘤具有高PD-L1表达(总比例评分(TPS)≥50%),且无敏感EGFR/ALK改变.最后,对于其余约50％的患者，他们的肿瘤没有或低PD-L1表达（TPS为0-49％），并且没有敏感的EGFR/ALK异常，与单独化疗相比,单独添加PD-1/L1抑制剂或联合添加细胞毒性T淋巴细胞相关蛋白4(CTLA-4)抑制剂的含铂化疗可改善PFS和OS.这篇综述的目的是总结目前对不可切除的NSCLC患者进行一线全身治疗的数据和观点，并提出一种在诊断时实施精确生物标志物测试的实用算法。
