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

Toby Trahair; Andrew J Gifford; Ashleigh Fordham; Chelsea Mayoh; Mitali Fadia; Robyn Lukeis; Andrew C Wood; Santosh Valvi; Roderick D Walker; James Blackburn; Erin E Heyer; Tim R Mercer; Draga Barbaric; Glenn M Marshall; Karen L MacKenzie

doi:10.1200/PO.18.00297

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

JCO Precis Oncol. 2019 May 16:3:PO.18.00297. doi: 10.1200/PO.18.00297. eCollection 2019.

Authors

Toby Trahair^{1

2

3}, Andrew J Gifford^{2

4}, Ashleigh Fordham², Chelsea Mayoh², Mitali Fadia^{5

6}, Robyn Lukeis⁷, Andrew C Wood⁸, Santosh Valvi⁹, Roderick D Walker¹⁰, James Blackburn^{3

11}, Erin E Heyer¹¹, Tim R Mercer^{3

11

12}, Draga Barbaric¹, Glenn M Marshall^{1

2

3}, Karen L MacKenzie¹³

Affiliations

¹ Sydney Children's Hospital, Randwick, New South Wales, Australia.
² Children's Cancer Institute, Sydney, New South Wales, Australia.
³ University of New South Wales, Sydney, New South Wales, Australia.
⁴ Prince of Wales Hospital, Randwick, New South Wales, Australia.
⁵ Canberra Hospital, Garran, Australian Capital Territory, Australia.
⁶ Australian National University Medical School, Acton, Australian Capital Territory, Australia.
⁷ St Vincent's Hospital, Darlinghurst, New South Wales, Australia.
⁸ University of Auckland, Auckland, New Zealand.
⁹ Perth Children's Hospital, Perth, Western Australia, Australia.
¹⁰ Queensland Children's Hospital, South Brisbane, Queensland, Australia.
¹¹ Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
¹² Altius Institute for Biomedical Sciences, Seattle, WA.
¹³ Children's Medical Research Institute, Westmead New South Wales, Australia.

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.