Guo Matthew Z, Marrone Kristen A, Spira Alexander, Waterhouse David M, Scott Susan C
Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Virginia Cancer Specialists Research Institute, Fairfax, VA, USA.
Onco Targets Ther. 2021 Nov 23;14:5321-5331. doi: 10.2147/OTT.S273357. eCollection 2021.
dysregulation promoting tumorigenesis in non-small cell lung cancer (NSCLC) is associated with worse outcomes following chemotherapy as compared to non-driver mutated NSCLC and occurs either through mutations causing exon 14 skipping (ex14) or gene amplification and overexpression that result in enhanced receptor signaling. Capmatinib is the first FDA-approved targeted therapy for NSCLC with ex14 skipping mutations, approved in 2020. FoundationOne CDx, a comprehensive genomic profiling test for solid tumors, was concurrently approved as a companion diagnostic for capmatinib use. The GEOMETRY mono-1 phase II trial of capmatinib monotherapy demonstrated an overall response rate (ORR) of 68% in treatment naïve (n=28) and 41% in pre-treated (n=69) ex14 skipping advanced NSCLC; in amplified advanced NSCLC (gene copy number ≥ 10) ORRs of 40% in treatment naïve and 29% in pre-treated disease was seen. This review outlines the clinical data supporting capmatinib approval in the treatment of NSCLC and FoundationOne CDx approval as a companion diagnostic. We detail the practical clinical administration of capmatinib, including dosing and toxicity management, compare capmatinib to other approved and investigational MET-targeted therapies, discuss limitations of capmatinib, and highlight ongoing trials of capmatinib in combinatorial approaches.
与非驱动基因突变的非小细胞肺癌（NSCLC）相比，促进NSCLC肿瘤发生的失调与化疗后更差的预后相关，其发生机制要么是导致外显子14跳跃（ex14）的突变，要么是基因扩增和过表达，从而导致受体信号增强。卡马替尼是2020年美国食品药品监督管理局（FDA）批准的首个用于治疗具有ex14跳跃突变的NSCLC的靶向疗法。FoundationOne CDx是一种针对实体瘤的综合基因组分析检测，同时被批准作为卡马替尼使用的伴随诊断方法。卡马替尼单药治疗的GEOMETRY mono-1 II期试验表明，初治（n = 28）的ex14跳跃晚期NSCLC患者的总体缓解率（ORR）为68%，预处理（n = 69）患者的总体缓解率为41%；在基因扩增的晚期NSCLC（基因拷贝数≥10）中，初治患者的ORR为40%，预处理患者的ORR为29%。本综述概述了支持卡马替尼获批用于治疗NSCLC以及FoundationOne CDx获批作为伴随诊断方法的临床数据。我们详细介绍了卡马替尼的实际临床应用，包括给药和毒性管理，将卡马替尼与其他已批准和正在研究的MET靶向疗法进行比较，讨论卡马替尼的局限性，并强调卡马替尼联合治疗方法的正在进行的试验。
