Abstract
Background
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.
Ethical Statement
The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). This study was conducted with Fourth Hospital of Hebei Medical University Research Ethics Board approval ((2021KS005). Written informed consent was obtained from the patient’s family for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors have no conflicts of interest to declare for this work.