Multinational phase 1-2 study of pralsetinib for advanced RET fusion-positive NSCLC: final results from ARROW

RET fusions are observed in 1%-2% of non-small cell lung cancers (NSCLCs). The multinational phase 1-2 ARROW study evaluated the oral selective RET inhibitor pralsetinib 400 mg once daily in RET fusion-positive NSCLCs. Final results have now been published. At data lock, 281 patients initiated pralsetinib; the median treatment duration was 15.0 months. The objective response rate among the 259 patients with measurable disease was 78% (95% CI 69-86) for treatment-naïve patients and 63% (54-71) for prior platinum-based chemotherapy patients. The median overall survival was 44.3 months (95% CI 30.9-53.1) among all patients, 50.1 months (28.3-NR) among treatment-naïve patients, and 39.7 months (27.8-53.2) among prior platinum patients. Common grade ≥ 3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Twenty-nine patients (10%) discontinued pralsetinib, and 144 (51%) experienced dose reductions due to TRAEs. Three treatment-related deaths occurred associated with four TRAEs. The authors conclude that pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion-positive NSCLCs.