Sakamoto Mandy, Patil Tejas
Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA.
NPJ Precis Oncol. 2023 Jun 8;7(1):56. doi: 10.1038/s41698-023-00381-0.
Patients with ROS1-rearranged NSCLC demonstrate excellent disease control with ROS1-targeted therapy, but acquired resistance is inevitable. Of particular interest is the ROS1 L2086F kinase domain mutation which is refractory to all currently available ROS1 TKIs apart from cabozantinib. We present a case of a patient with metastatic ROS1-rearranged NSCLC with dual ROS1 F2004V and L2086F resistance mutations who radiographically responded to the combination of lorlatinib and cabozantinib in a patient with metastatic NSCLC. Furthermore, the patient experienced exceptional clinical improvement and tolerance with the combined use of lorlatinib and cabozantinib. This case builds the case for cabozantinib as an agent to overcome ROS1 L2086F resistance. It also highlights the efficacy and safety of using combination of ROS1 TKIs to overcome complex resistance patterns.
ROS1重排的非小细胞肺癌（NSCLC）患者接受ROS1靶向治疗后疾病控制良好，但获得性耐药不可避免。特别值得关注的是ROS1 L2086F激酶结构域突变，除卡博替尼外，对目前所有可用的ROS1酪氨酸激酶抑制剂（TKIs）均耐药。我们报告了1例转移性ROS1重排NSCLC患者，该患者存在ROS1 F2004V和L2086F双重耐药突变，影像学显示其对洛拉替尼和卡博替尼联合治疗有反应。此外，该患者在联合使用洛拉替尼和卡博替尼后临床症状显著改善且耐受性良好。该病例证明了卡博替尼可作为克服ROS1 L2086F耐药的药物。它还突出了联合使用ROS1 TKIs克服复杂耐药模式的有效性和安全性。
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