Safety and efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer including as first-line therapy

• Verfasst von: Griesinger, Frank [VerfasserIn]
• Verfasst von: Curigliano, G. [VerfasserIn]
• Verfasst von: Thomas, Michael [VerfasserIn]
• Verfasst von: Subbiah, V. [VerfasserIn]
• Verfasst von: Baik, C. S. [VerfasserIn]
• Verfasst von: Tan, D. S. W. [VerfasserIn]
• Verfasst von: Lee, D. H. [VerfasserIn]
• Verfasst von: Misch, D. [VerfasserIn]
• Verfasst von: Garralda, E. [VerfasserIn]
• Verfasst von: Kim, D. -W. [VerfasserIn]
• Verfasst von: van der Wekken, A. J. [VerfasserIn]
• Verfasst von: Gainor, J. F. [VerfasserIn]
• Verfasst von: Paz-Ares, L. [VerfasserIn]
• Verfasst von: Liu, S. V. [VerfasserIn]
• Verfasst von: Kalemkerian, G. P. [VerfasserIn]
• Verfasst von: Houvras, Y. [VerfasserIn]
• Verfasst von: Bowles, D. W. [VerfasserIn]
• Verfasst von: Mansfield, A. S. [VerfasserIn]
• Verfasst von: Lin, J. J. [VerfasserIn]
• Verfasst von: Smoljanovic, V. [VerfasserIn]
• Verfasst von: Rahman, A. [VerfasserIn]
• Verfasst von: Kong, S. [VerfasserIn]
• Verfasst von: Zalutskaya, A. [VerfasserIn]
• Verfasst von: Louie-Gao, M. [VerfasserIn]
• Verfasst von: Boral, A. L. [VerfasserIn]
• Verfasst von: Mazières, J. [VerfasserIn]
• Titel: Safety and efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer including as first-line therapy
• Titelzusatz: update from the ARROW trial
• Verf.angabe: F. Griesinger, G. Curigliano, M. Thomas, V. Subbiah, C.S. Baik, D.S.W. Tan, D.H. Lee, D. Misch, E. Garralda, D.-W. Kim, A.J. van der Wekken, J.F. Gainor, L. Paz-Ares, S.V. Liu, G.P. Kalemkerian, Y. Houvras, D.W. Bowles, A.S. Mansfield, J.J. Lin, V. Smoljanovic, A. Rahman, S. Kong, A. Zalutskaya, M. Louie-Gao, A.L. Boral & J. Mazières
• E-Jahr: 2022
• Jahr: 13 August 2022
• Umfang: 11 S.
• Fussnoten: Gesehen am 19.01.2023
• Titel Quelle: Enthalten in: Annals of oncology
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1990
• Jahr Quelle: 2022
• Band/Heft Quelle: 33(2022), 11 vom: Nov., Seite 1168-1178
• ISSN Quelle: 1569-8041
• DOI: doi:10.1016/j.annonc.2022.08.002
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: frontline therapy
• Sach-SW: non-small-cell lung cancer
• Sach-SW: pralsetinib
• Sach-SW: RET fusion
• Sach-SW: RET inhibition
• Sach-SW: targeted therapy
• K10plus-PPN: 1831538326

Abstract

Background - RET fusions are present in 1%-2% of non-small-cell lung cancer (NSCLC). Pralsetinib, a highly potent, oral, central nervous system-penetrant, selective RET inhibitor, previously demonstrated clinical activity in patients with RET fusion-positive NSCLC in the phase I/II ARROW study, including among treatment-naive patients. We report an updated analysis from the ARROW study. - Patients and methods - ARROW is a multi-cohort, open-label, phase I/II study. Eligible patients were ≥18 years of age with locally advanced or metastatic solid tumours and an Eastern Cooperative Oncology Group performance status of 0-2 (later 0-1). Patients initiated pralsetinib at the recommended phase II dose of 400 mg once daily until disease progression, intolerance, consent withdrawal, or investigator’s decision. The co-primary endpoints (phase II) were overall response rate (ORR) by blinded independent central review and safety. - Results - Between 17 March 2017 and 6 November 2020 (data cut-off), 281 patients with RET fusion-positive NSCLC were enrolled. The ORR was 72% [54/75; 95% confidence interval (CI) 60% to 82%] for treatment-naive patients and 59% (80/136; 95% CI 50% to 67%) for patients with prior platinum-based chemotherapy (enrolment cut-off for efficacy analysis: 22 May 2020); median duration of response was not reached for treatment-naive patients and 22.3 months for prior platinum-based chemotherapy patients. Tumour shrinkage was observed in all treatment-naive patients and in 97% of patients with prior platinum-based chemotherapy; median progression-free survival was 13.0 and 16.5 months, respectively. In patients with measurable intracranial metastases, the intracranial response rate was 70% (7/10; 95% CI 35% to 93%); all had received prior systemic treatment. In treatment-naive patients with RET fusion-positive NSCLC who initiated pralsetinib by the data cut-off (n = 116), the most common grade 3-4 treatment-related adverse events (TRAEs) were neutropenia (18%), hypertension (10%), increased blood creatine phosphokinase (9%), and lymphopenia (9%). Overall, 7% (20/281) discontinued due to TRAEs. - Conclusions - Pralsetinib treatment produced robust efficacy and was generally well tolerated in treatment-naive patients with advanced RET fusion-positive NSCLC. Results from the confirmatory phase III AcceleRET Lung study (NCT04222972) of pralsetinib versus standard of care in the first-line setting are pending.