Abstract
ALK rearrangements define an important molecular subtype of lung adenocarcinoma, and the rearranged ALK serves as a well-established oncogenic driver in this malignancy. The most common type of mutation is the EML4-ALK fusion. Meanwhile, rare fusions are also frequently discovered with regard to ALK. However, clinical efficacy varies substantially across rare ALK fusion variants due to their distinct biological features, and individualized drug selection guided by fusion architecture and tumor characteristics is therefore required. This case presents the entire treatment process of a female patient with advanced lung adenocarcinoma who had an OSBPL9-ALK fusion. The patient was diagnosed in early 2021; by referring to previous reports and model prediction with AlphaFold 2 and Autodock Pymol, the new second-generation ALK inhibitor Ensartinib was chosen. After 24 months, due to disease progression, she switched to the third-generation ALK inhibitor, Lorlatinib, after model prediction. After 15 months, for further disease progression, the anti-angiogenic drug, anlotinib, was added to the treatment plan. Unfortunately, 6 months later, the disease progressed further, and the patient chose supportive treatment for economic reason. Nine months later, the patient died. The presentation of this case will provide a reference guideline for the subsequent treatment of lung adenocarcinoma with the same fusion. Meanwhile, model-based prediction for ALK fusion targeted therapy can provide a predictive reference for drug selection in patients presenting similar ALK rearrangements in the future.