Impact of ALK inhibitors in patients with ALK-pearranged nonlung solid tumors

Yuki Takeyasu, Hitomi S. Okuma, Yuki Kojima, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Tatsunori Shimoi, Emi Noguchi, Ayumu Arakawa, Taisuke Mori, Kuniko Sunami, Takashi Kubo, Takashi Kohno, Yoshida Akihiko, Noboru Yamamoto, Kan Yonemori

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALKrearranged nonlung solid tumors.

Original languageEnglish
Pages (from-to)756-766
Number of pages11
JournalJCO Precision Oncology
Publication statusPublished - 2021
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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