近年来,非小细胞肺癌(NSCLC)的复杂治疗策略发生了重大变化。在围手术期治疗中注册的免疫疗法和化学疗法的无病生存率显着增加,以及EGFR突变的辅助注册免疫疗法和靶向治疗(奥希替尼)。在致癌成瘾的转移性NSCLC中,主要是腺癌,靶向治疗的范围正在扩大,预期的总体生存率显着增加,以年衡量。到2021年,FDA和EMA已经批准靶向药物来抑制EGFR激活突变。T790M抗性突变,BRAFV600E突变,ALK,ROS1、NTRK和RET融合。2022年,授权靶向治疗的范围扩大。使用抑制KRASG12C的疗法,EGFR外显子20、HER2和MET。直到现在,KRAS突变没有注册靶向治疗,影响30%的腺癌.因此,最大的期望围绕KRASG12C突变的抑制,发生在15%的非小细胞肺癌中,主要是吸烟者,其特点是预后不良。Sotorasib和adagrasib在至少一个先前的化疗和/或免疫疗法疗程后被批准为二线药物。Adagrasib与pembrolizumab免疫疗法的一线组合被证明更有益,尤其是PD-L1高表达的患者。在肺腺癌EGFR外显子20插入突变中,Amivantanab在铂类化疗后被登记为进展.肺腺癌携带EGFR外显子20,HER2插入突变2%,第一个靶向治疗是曲妥珠单抗deruxtecan,已经接受铂类药物化疗的患者。两种口服选择性c-MET抑制剂,卡马替尼和替泊替尼,在携带约3%的MET外显子14跳跃突变的腺癌中,化疗后也被批准。将反射测试与下一代测序(NGS)相结合,通过识别指南推荐的分子改变来扩展个性化治疗。
The complex therapeutic strategy of non-small cell lung cancer (NSCLC) has changed significantly in recent years. Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation. In oncogenic-addictive metastatic NSCLC, primarily in adenocarcinoma, the range of targeted therapies is expanding, with which the expected overall survival increases significantly, measured in years. By 2021, the FDA and EMA have approved targeted agents to inhibit EGFR activating mutations, T790 M resistance mutation, BRAF V600E mutation, ALK, ROS1, NTRK and RET fusion. In 2022, the range of authorized target therapies was expanded. With therapies that inhibit KRASG12C, EGFR exon 20, HER2 and MET. Until now, there was no registered targeted therapy for the KRAS mutations, which affect 30% of adenocarcinomas. Thus, the greatest expectation surrounded the inhibition of the KRAS G12C mutation, which occurs in ∼15% of NSCLC, mainly in smokers and is characterized by a poor prognosis. Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1. In EGFR exon 20 insertion mutation of lung adenocarcinoma, amivantanab was registered for progression after platinum-based chemotherapy. Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations.