Durable response with mutation-guided ALK inhibition in a patient with metastatic epithelioid inflammatory...

Anaplastic lymphoma kinase (ALK) alterations, including activating mutations, amplifications, and fusions/rearrangements, are found in approximately 3.3% of cancers, including over 50% of inflammatory myofibroblastic tumors. Tyrosine kinase inhibitors to target ALK have significant activity against ALK-mutant cancers, including next generation inhibitors to combat frequent resistance. Here, we present a patient diagnosed with high grade metastatic inflammatory myofibroblastic tumor driven by a RANBP2::ALK fusion, who later developed an ALK G1202R resistance mutation in the setting of treatment with crizotinib. Upon changing therapy to lorlatinib, which is effective against this mutation in lung cancer, the patient again achieved a response that permitted surgical resection. The patient remains without evidence of disease now 18 months after discontinuing adjuvant lorlatinib. This case illustrates the importance of serial molecular profiling to guide selection of the optimal ALK inhibitor for the best clinical outcomes.