自2011年以来，美国FDA已批准30个新药用于晚期非小细胞肺癌（NSCLC），主要包括酪氨酸激酶抑制剂和免疫检查点抑制剂。具有癌基因驱动基因改变的非小细胞肺癌适合用靶向药物（通常是小分子抑制剂）治疗。在这些案例中，由于单队列或多队列试验显示出较高的总体反应率，加上持久的反应时间，因此可以在美国加速批准。随后通过上市后试验提供了确凿的临床证据。对于没有此类驱动因素改变的非小细胞肺癌，美国和欧盟的监管机构设定了临床证据期望，促进基于随机对照试验设计的研究的进行，主要侧重于确定生存期或无事件生存期。本综述分析了非小细胞肺癌新疗法的批准模式，重点关注针对驱动改变的小分子抑制剂以及生物制品。后者包括抑制 PD-(L)1 等免疫检查点或细胞表面受体的单克隆抗体，以及抗体-药物偶联物，即与细胞毒性化合物连接的高效生物制剂。 NSCLC 的癌基因成瘾亚型和非癌基因成瘾亚型的分化决定了药物开发策略、临床开发计划的范围、获得孤儿药开发激励措施以及监管审批策略。

Since 2011, the U.S. FDA has approved 30 new drugs for use in advanced non-small-cell lung cancer (NSCLC), mainly comprising tyrosine kinase inhibitors and immune checkpoint inhibitors. NSCLC with oncogene driver alterations is amenable to treatment with targeted drugs, usually small molecule inhibitors. In these cases, the demonstration of high overall response rates, coupled with a lasting duration of response, has allowed for accelerated approval in the U.S., based on single or multi-cohort trials. Confirmatory clinical evidence was subsequently provided through post-marketing trials. In NSCLC without such driver alterations, regulatory agencies in both the U.S. and the EU set clinical evidence expectations that foster the conduct of studies primarily focused on determining survival or event-free survival, based on randomized-controlled trial designs. This review analyzes the approval patterns of novel therapeutics for NSCLC with a focus on small molecule inhibitors that target driver alterations, as well as biologicals. The latter include monoclonal antibodies inhibiting immune checkpoints like PD-(L)1 or cell surface receptors, and antibody-drug conjugates, highly potent biologics linked to a cytotoxic compound. The differentiation of NSCLC into oncogene- and non-oncogene-addicted subtypes determines drug development strategies, the extent of the clinical development program, access to orphan drug development incentives, and regulatory approval strategies.