Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced RET Fusion–Positive Non–Small Cell Lung Cancer

作者：Benjamin Besse, Vivek Subbiah, G. Curigliano, Daniel W. Bowles, Robert C. Doebele, Aaron S. Mansfield, Christina S. Baik, Gilberto Lopes, Luis Paz-Ares, Matthew H. Taylor, Daniel S.W. Tan, G. Alonso, Shirish M. Gadgeel, Gregory P. Kalemkerian, S.-H.I. Ou, Anthonie J. van der Wekken, Carlos R. Becerra, Makenzi Colleen Evangelist, Frank Griesinger, Stephen V. Liu, Yanyan Lou, Julien Mazières, Jason M. Melear, Mohit Narang, Ashish Saxena, Michael Thomas, Sophia Y. Wang, Amber Thomassen, Dae Ho Lee, Dong-Wan Kim, Justin F. Gainor · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco-25-01489 · 被引用次数：2 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment、Thyroid Cancer Diagnosis and Treatment

RET fusions appear in 1%-2% of non–small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385 ) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET -altered NSCLC and RET fusion–positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion–positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageabl...