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Ref Type Journal Article
PMID (34036223)
Authors Takeyasu Y, Okuma HS, Kojima Y, Nishikawa T, Tanioka M, Sudo K, Shimoi T, Noguchi E, Arakawa A, Mori T, Sunami K, Kubo T, Kohno T, Akihiko Y, Yamamoto N, Yonemori K
Title Impact of ALK Inhibitors in Patients With ALK-Rearranged Nonlung Solid Tumors.
Journal JCO precision oncology
Vol 5
Issue
Date 2021
URL
Abstract Text Anaplastic lymphoma kinase (ALK) rearrangement is a well-known driver oncogene in non-small-cell lung cancer and has also been identified in other types of tumors. However, there is limited evidence on the clinical response to ALK tyrosine kinase inhibitors (TKIs), such as alectinib and crizotinib, in rare tumors with ALK fusion. We evaluated the therapeutic effect of ALK-TKIs in rare ALK-rearranged tumors.Between April 2012 and April 2019, clinical outcomes and characteristics of patients with ALK-rearranged nonlung solid tumors who received ALK-TKIs (alectinib and/or crizotinib) outside of clinical trials were reviewed. Expression and/or rearrangement of ALK was evaluated by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. The tumor response was assessed according to RECIST (version 1.1). Progression-free survival was estimated from initial ALK-TKI initiation until progression.We identified seven patients (inflammatory myofibroblastic tumors, n = 3; ALK-positive histiocytosis, n = 1; histiocytic sarcoma, n = 1; osteosarcoma, n = 1; and parotid adenocarcinoma, n = 1), with a median age of 17 years. Two rare ALK fusions, namely, CTNNA1-ALK and ITSN2-ALK, were identified. As initial ALK-TKI therapy, five patients received alectinib and two received crizotinib. The objective response rate for the initial ALK-TKI therapy was 85.7% (95% CI, 44 to 97), including two patients who received alectinib and achieved complete response. The median progression-free survival was 8.1 months (range, 1.7 to not estimable). There were no treatment interruptions or dose reductions because of adverse events caused by alectinib.This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALK-rearranged nonlung solid tumors.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK rearrange inflammatory myofibroblastic tumor sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 40 months in a pediatric patient with an ALK-rearranged inflammatory myofibroblastic tumor (PMID: 34036223). 34036223
ALK rearrange epithelioid inflammatory myofibroblastic sarcoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response lasting 44.2 months in a pediatric patient with an ALK-rearranged epithelioid inflammatory myofibroblastic tumor (PMID: 34036223). 34036223