| Summary: | Dan Li, Jiayin Liu, Xue Zhang, Jing Han, Hui Jin, Long Wang, Li Feng, Zhisong Fan, Jing Zuo, Yudong Wang Department of Medical Oncology, The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yudong Wang, Department of Medical Oncology, The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, 12 Jiankang Road, Shijiazhuang, People’s Republic of China, Tel +86 15931166600, Email 15931166600@126.comBackground: Lorlatinib has been suggested as the therapeutic option for patients with ROS1-rearranged non-small-cell lung cancer (NSCLC) after ROS1 tyrosine kinase inhibitor (TKI) failure. However, the mechanism mediating lorlatinib resistance has not been well elucidated in ROS1-rearranged NSCLC. Post- lorlatinib therapeutic options remain scarce.Case Presentation: Herein, we describe a 31-year-old female patient with stage IVB ROS1-rearranged NSCLC. She received 2nd line treatment with crizotinib after chemotherapy failure and achieved a partial response lasting for 15 months. An NF1 p.G127Ter mutation emerged as a potential crizotinib resistance mechanism. She subsequently received lorlatinib treatment and achieved a progression-free survival (PFS) of seven months. Based on the emergence of a resistant BRAF V600E, the patient was switched to a combinatorial targeted therapy with lorlatinib, dabrafenib, and trametinib and attained stable disease. She continued the treatment with a time-to-treatment failure of 5.5 months. The acquisition of NRAS p.Q61R and NTRK amplification may confer resistance to the combinatorial targeted therapy.Conclusion: To the best of our knowledge, we reported the first case demonstrating that BRAF p.V600E can mediate the lorlatinib resistance in ROS1-rearranged NSCLC and the combinational targeted therapy of ROS1 TKI with dabrafenib and trametinib may serve as an efficient therapeutic option for subsequent treatment.Keywords: NSCLC, ROS1 rearrangement, BRAF V600E, lorlatinib combined with dabrafenib and trametinib, case report
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