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Ref Type Journal Article
PMID (42150148)
Authors Abreu de Góes V, Lee M, Zugman M, Moradi A, Jaime-Casas S, Shah K, Jun Li Y, V Castro D, Li X, Mercier B, Hsu J, Chehrazi-Raffle A, Doctor V, Moran A, Markman M, Shreenivas A, Pal SK
Title Use of ALK Inhibitors in Patients With Nonlung Malignancies Bearing ALK Alteration Prolongs Treatment Duration.
Journal Vol Issue Date Pages Journal Short Title
JCO precision oncology 10 5 2026 May e2600121 JCO Precis Oncol
URL
Abstract Text Anaplastic lymphoma kinase (ALK) inhibitors are known to produce deep responses in selected cancer types. However, data on their use outside of these types are scarce. We evaluated outcomes of these drugs for tumor types without current (US) Food and Drug Administration approval.We collected data on patients who received ALK inhibitors between January 1, 2013, and June 1, 2025. We excluded patients with non-small cell lung cancer, anaplastic large cell lymphoma, and inflammatory myofibroblastic tumors and those treated in a clinical trial. Descriptive analyses summarized patients' characteristics, molecular profiles, and treatment patterns. We compared the time to treatment failure (TTF) between ALK-therapy and the treatment immediately preceding it. We also assessed real-world radiographic responses on ALK inhibitors and the overall survival (OS) for the cohort. Given the small number of patients, we conducted exploratory subgroup analysis.A total of 19 patients were included. The most common histologies were sarcomas (26%) and papillary renal cell carcinoma (16%). Most patients (73%) had two or more metastatic sites at baseline, often harboring ALK fusions (68%). ALK inhibitors were administered as third-line therapy or later in 52% of patients, with alectinib being the most common (52%). The median TTF with ALK therapy was 9.1 months (95% CI, 3.3 to 13.3), compared with 2.6 months (95% CI, 1.6 to 5.5) for the previous line. Among 15 patients with imaging, 53.3% had partial responses and 26.7% had stable disease. The median OS was 9.1 months (95% CI, 3.3 to 13.3).ALK inhibitors were associated with longer TTF in comparison with their prior therapies. This supports the rationale for their agnostic use for tumors where clinical trials are not feasible.

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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 R1275L neuroblastoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response with a time to treatment failure of 10.3 months in a patient with neuroblastoma harboring ALK R1275L (reported as ALK c.3824G>T) (PMID: 42150148). 42150148
EML4 - ALK salivary gland carcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response with a time to treatment failure of 9.5 months in a patient with salivary gland adenocarcinoma harboring EML4-ALK (PMID: 42150148). 42150148
EML4 - ALK spindle cell sarcoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, treatment with Xalkori (crizotinib) resulted in a partial response in a patient with myxoid spindle cell tumor harboring EML4-ALK (PMID: 42150148). 42150148
ALK amp rhabdomyosarcoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response with a time to treatment failure of 9.5 months in a patient with ALK-amplified rhabdomyosarcoma (PMID: 42150148). 42150148
EML4 - ALK papillary renal cell carcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in 2 partial responses with a time to treatment failure of 21.9 months and 24.4 months among 2 patients with papillary renal cell carcinoma harboring EML4-ALK (PMID: 42150148). 42150148
EML4 - ALK clear cell renal cell carcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response with a time to treatment failure of 6.9 months in a patient with clear cell renal cell carcinoma harboring EML4-ALK (PMID: 42150148). 42150148