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
Recommended Citation
Besse B, Subbiah V, Curigliano G, Bowles DW, Doebele RC, Mansfield AS, Baik CS, de Lima Lopes G, Paz-Ares L, Taylor MH, Tan DSW, Alonso G, Gadgeel SM, Kalemkerian GP, Ou SI, van der Wekken AJ, Becerra CR, Evangelist M, Griesinger F, Liu SV, Lou Y, Mazières J, Melear JM, Narang M, Saxena A, Thomas M, Wang S, Thomassen A, Lee DH, Kim DW, Gainor JF. 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. J Clin Oncol. 2026;44(13):1190-1197.
Document Type
Article
Publication Date
5-1-2026
Publication Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Keywords
Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Female, Proto-Oncogene Proteins c-ret, Male, Middle Aged, Aged, Adult, Pyrazoles, Pyrimidines, Pyridines, Oncogene Proteins, Fusion, Aged, 80 and over, Protein Kinase Inhibitors, Progression-Free Survival
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.
Medical Subject Headings
Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Female; Proto-Oncogene Proteins c-ret; Male; Middle Aged; Aged; Adult; Pyrazoles; Pyrimidines; Pyridines; Oncogene Proteins, Fusion; Aged, 80 and over; Protein Kinase Inhibitors; Progression-Free Survival
PubMed ID
41886723
ePublication
ePub ahead of print
Volume
44
Issue
13
First Page
1190
Last Page
1197
