Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced <i>RET</i> Fusion–Positive Non–Small Cell Lung Cancer
Abstract
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 manageable safety in treatment-naïve and previously treated patients with RET fusion–positive NSCLCs, confirming previous findings with longer follow-up.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (31)
Benjamin Besse
Vivek Subbiah
Giuseppe Curigliano
Daniel W. Bowles
University of Colorado Cancer Center, Aurora, CO
Robert C. Doebele
Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO
Aaron S. Mansfield
Christina S. Baik
Thoracic, Head and Neck Medical Oncology, Fred Hutchinson Cancer Center, University of Washington, Seattle
Gilberto de Lima Lopes
Sylvester Comprehensive Cancer Center at the University of Miami and the Miller School of Medicine Miami Florida USA
Luis Paz-Ares
Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid
Matthew H. Taylor
Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR
Daniel S.W. Tan
Division of Medical Oncology, National Cancer Centre Singapore and Duke-NUS Medical School, Singapore, Singapore
Guzman Alonso
Shirish M. Gadgeel
Division of Hematology-Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit
Gregory P. Kalemkerian
Department of Medicine, Hematology-Oncology, University of Michigan, Ann Arbor, MI
Sai-Hong Ignatius Ou
University of California, Irvine School of Medicine, Orange
Anthonie J. van der Wekken
Department of Pulmonology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
Carlos R. Becerra
Hoag Family Cancer Institute, Newport Beach, CA
Makenzi Evangelist
New York Oncology Hematology, Albany, NY
Frank Griesinger
Department of Hematology and Oncology, Pius Hospital, University Medicine Oldenburg, Oldenburg, Germany
Stephen V. Liu
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
Yanyan Lou
Julien Mazières
Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France
Jason M. Melear
Texas Oncology PA, Austin, TX
Mohit Narang
Ashish Saxena
Michael Thomas
Sophia Wang
Department of Mechanical and Aerospace Engineering, University of California Los Angeles
Amber Thomassen
11Rigel Pharmaceuticals, Inc., South San Francisco, United States
Dae Ho Lee
Dong-Wan Kim
School of Civil, Environmental and Architectural Engineering, Korea University, Seoul 02841, Republic of Korea
Justin F. Gainor