Abstract
PURPOSEAnaplastic 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.PATIENTS AND METHODSBetween 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.RESULTSWe 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.CONCLUSIONThis study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALK-rearranged nonlung solid tumors.
Highlights
Anaplastic lymphoma kinase (ALK) rearrangement was first discovered as a potential actionable therapeutic oncogenic gene aberration in anaplastic largecell lymphoma (ALCL).[1]
The objective response rate for the initial ALK-tyrosine kinase inhibitor (TKI) therapy was 85.7%, including two patients who received alectinib and achieved complete response
The first-generation ALK-tyrosine kinase inhibitor (TKI) to be approved following clinical trials was crizotinib, which acts as a mesenchymal epithelial transition factor and receptor tyrosine kinase-1 kinase inhibitor
Summary
Among the patients treated with an ALK-TKI outside of a clinical trial during the study period, seven had nonlung solid tumors. Initial ALK-TKI treatment consisted of alectinib in five patients and crizotinib in two patients. The ALK staining patterns were nuclear membranous in patient 3 with IMT (epithelioid), plasma membranous in patient 7 with parotid adenocarcinoma, and cytoplasmic in the remaining patients (Table 2 and Fig 1). All seven patients showed an ALK rearrangement of some kind, and four patients were tested by NGS In one 17-year-old patient with locally advanced bladder IMT (patient 2 in Table 2), it was possible to preserve the bladder because of the good response to crizotinib.[22] Three patients were treated with a second ALK-TKI, either alectinib or ceritinib. One patient receiving crizotinib experienced grade 3 neutropenia that was considered to be drug related, and dose reduction was required
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