Safety and efficacy of pralsetinib in RET fusion–positive non-small-cell lung cancer including as first-line therapy
| Autor: | 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 |
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| Přispěvatelé: | Institut Català de la Salut, [Griesinger F] Department of Hematology and Oncology, Pius-Hospital, University of Oldenburg, Oldenburg, Germany. [Curigliano G] European Institute of Oncology, IRCCS, Milan, Italy. Department of Oncology and Hemato-Oncology, University of Milano, Milan, Italy. [Thomas M] Department of Thoracic Oncology, Thoraxklinik, University Heidelberg and Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany. [Subbiah V] Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, USA. [Baik CS] Division of Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, USA. [Tan DSW] Division of Medical Oncology, National Cancer Centre Singapore, Singapore. [Garralda E] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Otros calificadores::/uso terapéutico [Otros calificadores]
Medicaments antineoplàstics - Ús terapèutic Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Hematology Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma Bronchogenic::Carcinoma Non-Small-Cell Lung [DISEASES] neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES] Other subheadings::Other subheadings::/drug therapy [Other subheadings] Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] targeted therapy Oncology non-small-cell lung cancer pralsetinib Avaluació de resultats (Assistència sanitària) Other subheadings::/therapeutic use [Other subheadings] Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] Pulmons - Càncer - Tractament frontline therapy RET fusion RET inhibition |
| Zdroj: | Scientia Annals of Oncology, 33(11), 1168-1178. Oxford University Press |
| ISSN: | 0923-7534 |
| Popis: | RET inhibition; Pralsetinib; Targeted therapy Inhibición de RET; Pralsetinib; Terapia dirigida Inhibició de RET; Pralsetinib; Teràpia dirigida 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. This work was supported by Blueprint Medicines Corporation and F. Hoffmann-La Roche, Ltd, Switzerland (no grant number). |
| Databáze: | OpenAIRE |
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