Use of ALK Inhibitors in Patients With Nonlung Malignancies Bearing ALK Alteration Prolongs Treatment Duration

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.