Zhang Hui, Wang Yong, Wu Huaguo, Zhou Shizhen, Li Shuo, Meng Xiangji, Tao Rongjie, Yu Jinming
Tianjin Cancer Institute, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China.
Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China.
Front Oncol. 2022 Apr 14;12:877279. doi: 10.3389/fonc.2022.877279. eCollection 2022.
Lung cancer patients with brain and leptomeningeal metastases usually have poor prognosis. For those patients with EGFR mutations, osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the first choice of treatment. However, drug resistance to osimertinib frequently occurs; and to date, the available follow-up treatment strategies have limited efficacy. In this case study, we report that treatments with olaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor, combined with dacomitinib, a second-generation EGFR TKI, benefited a lung cancer patient with osimertinib-resistant brain and leptomeningeal metastases. This 55-year-old male patient was found to have a pL858R mutation on EGFR exon 21 combined with TP53 and ERBB2 mutations after developing drug resistance to osimertinib treatment. Based on the genetic testing results, he was treated with olaparib and dacomitinib, and obtained 6 months of progression-free survival (PFS) and 13 months of overall survival (OS) after the diagnosis of leptomeningeal metastasis. This case report represents the first study applying PARP inhibitor in combination with dacomitinib in the treatment of leptomeningeal metastases after osimertinib resistance.
患有脑转移和软脑膜转移的肺癌患者通常预后较差。对于那些具有表皮生长因子受体（EGFR）突变的患者，第三代酪氨酸激酶抑制剂（TKI）奥希替尼是首选治疗药物。然而，对奥希替尼的耐药性经常出现；迄今为止，现有的后续治疗策略疗效有限。在本病例研究中，我们报告了使用聚（ADP - 核糖）聚合酶（PARP）抑制剂奥拉帕利联合第二代EGFR TKI达可替尼治疗一名对奥希替尼耐药的脑转移和软脑膜转移肺癌患者取得了良好效果。这名55岁男性患者在对奥希替尼治疗产生耐药性后，被发现EGFR外显子21上存在pL858R突变，同时伴有TP53和ERBB2突变。根据基因检测结果，他接受了奥拉帕利和达可替尼治疗，在诊断为软脑膜转移后获得了6个月的无进展生存期（PFS）和13个月的总生存期（OS）。本病例报告是第一项关于应用PARP抑制剂联合达可替尼治疗奥希替尼耐药后软脑膜转移的研究。
