Crizotinib and Surgery for Long-Term Disease Control in Children and Adolescents With ALK-Positive Inflammatory Myofibroblastic Tumors

Date

2019

Authors

Trahair, Toby
Gifford, Andrew J.
Fordham, Ashleigh
Mayoh, Chelsea
Fadia, Mitali
Lukeis, Robyn
Wood, A
Valvi, Santosh
Walker, Roderick D.
Blackburn, James

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Volume Title

Publisher

American Society of Clinical Oncology

Abstract

Purpose Before anaplastic lymphoma kinase (ALK) inhibitors, treatment options for ALK-positive inflammatory myofibroblastic tumors (AP-IMTs) were unsatisfactory. We retrospectively analyzed the outcome of patients with AP-IMT treated with crizotinib to document response, toxicity, survival, and features associated with relapse. Methods The cohort comprised eight patients with AP-IMT treated with crizotinib and surgery. Outcome measures were progression-free and overall survival after commencing crizotinib, treatment-related toxicities, features associated with relapse, outcome after relapse, and outcome after ceasing crizotinib. Results The median follow-up after commencing crizotinib was 3 years (range, 0.9 to 5.5 years). The major toxicity was neutropenia. All patients responded to crizotinib. Five were able to discontinue therapy without recurrence (median treatment duration, 1 year; range, 0.2 to 3.0 years); one continues on crizotinib. Two critically ill patients with initial complete response experienced relapse while on therapy. Both harbored RANBP2-ALK fusions and responded to alternative ALK inhibitors; one ultimately died as a result of progressive disease, whereas the other remains alive on treatment. Progression-free and overall survival since commencement of crizotinib is 0.75 ± 0.15% and 0.83 ± 0.15%, respectively. Conclusion We confirm acceptable toxicity and excellent disease control in patients with AP-IMT treated with crizotinib, which may be ceased without recurrence in most. Relapses occurred in two of three patients with RANBP2-ALK translocated IMT, which suggests that such patients require additional therapy.

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Citation

Source

JCO Precision Oncology

Type

Journal article

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Access Statement

Open Access

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Creative Commons Attribution licence

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