Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Japan.
Department of Biostatistics, Yokohama City University of Medicine, Yokohama, Japan.
Thorac Cancer. 2023 Sep;14(25):2622-2626. doi: 10.1111/1759-7714.15044. Epub 2023 Aug 6.
Entrectinib, a ROS-1 inhibitor, has been shown to be effective for patients with ROS-1 fused NSCLC, and has been established as the standard of care for this population. Entrectinib has been shown to achieve a better response to brain metastasis due to the characteristic of the drug having a weak interaction with P-glycoprotein and, even in prospective studies, the intracranial response is higher. Patients have been known to acquire resistance to molecularly targeted drugs such as EGF-TKIs or ALK-TKIs during targeted therapy. Similarly, the mechanisms of resistance to entrectinib have been reported, but information about the effects of TP53 mutation with entrectinib are still limited. Here, we experienced a case of a patient with ROS-1 fusion and concurrent TP53 mutation who was treated with entrectinib, resulting in a response to brain metastasis but rapid resistance to entrectinib. Our case demonstrates both the intracranial activity of entrectinib and the potential for resistance to entrectinib due to TP53 mutation.
恩曲替尼是一种 ROS-1 抑制剂，已被证明对 ROS-1 融合 NSCLC 患者有效，并已成为该人群的标准治疗方法。恩曲替尼由于与 P-糖蛋白的相互作用较弱，因此对脑转移有更好的反应，即使在前瞻性研究中，颅内反应也更高。在靶向治疗期间，患者已知会对 EGF-TKIs 或 ALK-TKIs 等分子靶向药物产生耐药性。同样，已经报道了对恩曲替尼产生耐药性的机制，但有关恩曲替尼与 TP53 突变的影响的信息仍然有限。在这里，我们遇到了一例 ROS-1 融合并伴有 TP53 突变的患者，该患者接受了恩曲替尼治疗，导致脑转移的反应，但对恩曲替尼迅速产生耐药性。我们的病例既展示了恩曲替尼的颅内活性，也展示了由于 TP53 突变而对恩曲替尼产生耐药性的潜力。
