Department of Geriatrics, 117865Tianjin Medical University General Hospital, People's Republic of China.
Department of Hematology, 117865Tianjin Medical University General Hospital, People's Republic of China.
J Oncol Pharm Pract. 2021 Dec;27(8):2007-2009. doi: 10.1177/10781552211044980. Epub 2021 Sep 27.
Epidermal growth factor receptor gene exon 20 insertion mutations are seen in ∼4-12% of patients with epidermal growth factor receptor-mutant non-small cell lung cancer. However, there is no targeted therapy approved for the treatment of non-small cell lung cancer patients with these rare epidermal growth factor receptor mutations. Previous studies revealed that epidermal growth factor receptor gene exon 20 insertion mutations are unique in their ability to activate epidermal growth factor receptor without the typical structural changes associated with the common epidermal growth factor receptor mutations, reducing the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors currently approved for non-small cell lung cancer. Therefore, there is an urgent need to identify active epidermal growth factor receptor-tyrosine kinase inhibitors and other effective treatment strategies for non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations. Mobocertinib is a novel irreversible epidermal growth factor receptor-tyrosine kinase inhibitor that selectively targets epidermal growth factor receptor gene exon 20 insertion mutations. Preclinical study revealed that mobocertinib inhibited the viability of epidermal growth factor receptor gene exon 20 insertion mutations-driven patient-derived xenografts and murine orthotopic tumors more potently than traditional epidermal growth factor receptor-tyrosine kinase inhibitors. In a study recently published in , Gonzalvez et al. assessed the safety, tolerability, and antitumor efficacy of mobocertinib in metastatic non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations. They found that non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations can benefit from mobocertinib treatment. Additionally, the treatment-related toxicity of mobocertinib was manageable. These findings lay the foundation for the application of mobocertinib in epidermal growth factor receptor gene exon 20 insertion-mutated non-small cell lung cancer.
表皮生长因子受体基因外显子 20 插入突变可见于约 4-12%的表皮生长因子受体突变型非小细胞肺癌患者。然而，目前尚无针对这些罕见表皮生长因子受体突变的非小细胞肺癌患者的靶向治疗药物获得批准。先前的研究表明，表皮生长因子受体基因外显子 20 插入突变具有独特的激活表皮生长因子受体的能力，而没有与常见表皮生长因子受体突变相关的典型结构变化，从而降低了目前批准用于非小细胞肺癌的表皮生长因子受体酪氨酸激酶抑制剂的临床疗效。因此，迫切需要为表皮生长因子受体基因外显子 20 插入突变的非小细胞肺癌患者确定有效的表皮生长因子受体酪氨酸激酶抑制剂和其他治疗策略。莫博赛替尼是一种新型的不可逆表皮生长因子受体酪氨酸激酶抑制剂，可选择性靶向表皮生长因子受体基因外显子 20 插入突变。临床前研究表明，莫博赛替尼对表皮生长因子受体基因外显子 20 插入突变驱动的患者来源异种移植和鼠原位肿瘤的抑制活性强于传统的表皮生长因子受体酪氨酸激酶抑制剂。在最近发表在《柳叶刀·肿瘤学》上的一项研究中，Gonzalvez 等人评估了莫博赛替尼在表皮生长因子受体基因外显子 20 插入突变的转移性非小细胞肺癌患者中的安全性、耐受性和抗肿瘤疗效。他们发现，表皮生长因子受体基因外显子 20 插入突变的非小细胞肺癌患者可从莫博赛替尼治疗中获益。此外，莫博赛替尼的治疗相关毒性是可管理的。这些发现为莫博赛替尼在表皮生长因子受体基因外显子 20 插入突变型非小细胞肺癌中的应用奠定了基础。
