Zaborowska-Szmi Magdalena, Szmit Sebastian, Krzakowski Maciej, Kowalski Dariusz M
Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Centre of Postgraduate Medical Education, Warsaw, Poland.
Drugs Today (Barc). 2023 Jan;59(1):17-36. doi: 10.1358/dot.2023.59.1.3425324.
Savolitinib is a highly selective MET tyrosine kinase inhibitor. MET is involved in numerous cellular processes such as proliferation, differentiation and the formation of distant metastases. MET amplification and MET overexpression are quite common in many cancers, but MET exon 14 skipping alteration is most common in non-small cell lung cancer (NSCLC). The role of MET signaling as a bypass pathway in the development of acquired resistance to tyrosine kinase inhibitor (TKI) epidermal growth factor receptor (EGFR) therapy in cancer patients with EGFR gene mutation was documented. Potential beneficiaries of savolitinib therapy are patients with NSCLC and initial diagnosis of MET ex 14 skipping mutation. Savolitinib therapy can be effective in NSCLC patients with EGFR-mutant MET with progression during first-line treatment with an EGFR-TKI. Antitumor activity of savolitinib in combination with osimertinib is very promising as first-line therapy of patients with advanced EGFR-mutated NSCLC, initially with MET expression. The safety profile of savolitinib as monotherapy and in combination with osimertinib or gefitinib is so favorable in all available studies that this drug has become a very promising therapeutic option and is being intensively investigated in ongoing clinical trials.
赛沃替尼是一种高度选择性的MET酪氨酸激酶抑制剂。MET参与众多细胞过程,如增殖、分化和远处转移的形成。MET扩增和MET过表达在许多癌症中相当常见,但MET第14外显子跳跃改变在非小细胞肺癌(NSCLC)中最为常见。已证明MET信号传导作为旁路途径在携带EGFR基因突变的癌症患者对酪氨酸激酶抑制剂(TKI)表皮生长因子受体(EGFR)治疗产生获得性耐药的过程中发挥作用。赛沃替尼治疗的潜在受益者是初诊为MET第14外显子跳跃突变的NSCLC患者。赛沃替尼治疗对在接受EGFR-TKI一线治疗期间病情进展的EGFR突变MET NSCLC患者可能有效。赛沃替尼与奥希替尼联合作为一线治疗晚期EGFR突变NSCLC且最初有MET表达患者的抗肿瘤活性非常有前景。在所有现有研究中,赛沃替尼单药治疗以及与奥希替尼或吉非替尼联合治疗的安全性都非常良好,以至于这种药物已成为一种非常有前景的治疗选择,并且正在正在进行的临床试验中进行深入研究。