- Immune checkpoint inhibitors (ICIs) are standard therapies in advanced NSCLC. Although genotype-directed tyrosine kinase inhibitors represent the standard of care for subsets of oncogene-driven NSCLC, patients may receive ICIs during their disease course. The impact of sequential ICI and tyrosine kinase inhibitor therapy on the risk of hepatotoxicity has not been described.
- ROS1 is a validated therapeutic target in NSCLC. In a phase I study, the multitargeted MET proto-oncogene, receptor tyrosine kinase/anaplastic lymphoma kinase/ROS1 inhibitor crizotinib demonstrated remarkable efficacy in ROS1-rearranged NSCLCs and consequently gained approval by the United States Food and Drug Administration and by the European Medicines Agency in 2016. However, similar to other oncogene-driven lung cancers, ROS1-rearranged lung cancers treated with crizotinib eventually acquire resistance, leading to disease relapse.
- The tyrosine kinase inhibitor crizotinib is an effective therapy for patients with cancers harboring rearrangements of the anaplastic lymphoma kinase (ALK) gene. Here, we describe two patients with advanced ALK-positive lung cancer who developed hypersensitivity to crizotinib, requiring temporary discontinuation of the drug. Both patients were treated with a rapid oral desensitization protocol allowing them to resume crizotinib without further signs or symptoms of hypersensitivity.