在携带ALK改变的非肺部恶性肿瘤患者中使用ALK抑制剂可延长治疗持续时间

Introduction ALK inhibitors are known to produce deep and durable responses in selected cancer types. However, data on their agnostic use are scarce, and the rarity of ALK alterations hinders clinical trial feasibility. We evaluated real-world outcomes of these drugs in tumor types without current FDA approval. Methods We collected clinical and genomic data on patients who received off-label ALK inhibitors between January 1st, 2013, and December 31, 2024, through electronic medical records at a single institution. Descriptive analyses were used to summarize patients' characteristics and treatment patterns. We compared the time to treatment failure (TTF) on ALK-targeted therapy and on its prior line of therapy, as well as radiographic response as evaluated by the provider or radiology report. Results A total of 19 patients were included. The median age at therapy start was 62 years, with 63% Caucasian and 31% Asian. The most common histologies were sarcomas (5/19), papillary renal cell carcinoma (3/19), and gastric adenocarcinoma (2/19). Most patients (73%) had two or more metastatic sites at treatment start, usually harboring ALK fusions (62%) or point mutations (21%). ALK inhibitors were administered as third-line or later in 52% of patients, with alectinib being the most common (52%), followed by crizotinib (36%). Prior treatments often included chemotherapy (58%), other tyrosine kinase inhibitors (32%), and checkpoint inhibitors (21%). The median TTF with ALK therapy was 6.7 months (95% CI, 3.3 - 21.9), compared to 2.6 months (95% CI, 1.6 - 5.5) for the previous line. Among 15 patients on ALK inhibitors with imaging, 7 had partial responses, 4 had stable disease, and 1 achieved a complete response. Conclusion ALK inhibitors improved clinical outcomes in comparison with prior therapies across several malignancies. This supports the rationale for its agnostic use for tumors where clinical trials are not feasible.