CHRONOS-4: phase 3 study of copanlisib plus rituximab-based immunochemotherapy in relapsed indolent B-cell lymphoma.

Autor:	Zinzani PL; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli,' Bologna, Italy.; Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy., Wang H; Department of Oncology, Tianjin Union Medical Centre, Nankai University, Tianjin, China., Feng J; Jiangsu Cancer Hospital, Nanjing, China., Kim TM; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea., Tao R; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Zhang H; Department of Medical Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China., Fogliatto L; Hematology and Hemotherapy Department, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., Maluquer Artigal C; Medical Hematology Department, Institut Catala d'Oncologia Hospitalet; Instituto de Investigación Biomédica de Bellvitge, Hospitalet de Llobregat, Universitat de Barcelona, Barcelona, Spain., Özcan M; Ankara University School of Medicine, Ankara, Turkey., Yanez E; Sociedad de Investigaciones Medicas Ltda, Temuco, Chile., Kim WS; Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea., Kirtbaya D; Oncology Dispensary No. 2, Sochi, Russia., Kriachok I; National Cancer Institute, Kiev, Ukraine., Maciel F; Division of Hematology, Transfusion Medicine and Cell Therapy, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Xue H; Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China., Bouabdallah K; Hematology and Cellular Therapy Department, University Hospital of Bordeaux, Bordeaux, France., Phelps C; Bayer HealthCare Pharmaceuticals Inc, Whippany, NJ., Chaturvedi S; Bayer HealthCare Pharmaceuticals Inc, Whippany, NJ., Weispfenning A; Bayer AG, Berlin, Germany., Morcos PN; Bayer HealthCare Pharmaceuticals Inc, Whippany, NJ., Odongo F; Bayer SA, São Paulo, Brazil., Buvaylo V; Bayer HealthCare Pharmaceuticals Inc, Whippany, NJ., Childs BH; Bayer HealthCare Pharmaceuticals Inc, Whippany, NJ., Dreyling M; Klinikum der Universität München LMU, Medizinische Klinik und Poliklinik III - Onkologie und Hämatologie, Munich, Germany., Matasar M; Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ., Ghione P; Memorial Sloan Kettering Cancer Center, New York, NY.; Weill Cornell Medical College, New York, NY.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Sep 24; Vol. 8 (18), pp. 4866-4876.
DOI:	10.1182/bloodadvances.2024013236
Abstrakt:	Abstract: Copanlisib, a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α and δ isoforms, previously demonstrated durable responses as monotherapy and improved progression-free survival (PFS) in combination with rituximab in patients with relapsed indolent non-Hodgkin lymphoma (iNHL). CHRONOS-4 was a phase 3, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of copanlisib in combination with standard immunochemotherapy in patients with relapsed iNHL. Patients (n = 524) were randomized (1:1) to copanlisib (60 mg IV) plus immunochemotherapy (rituximab and bendamustine [R-B] or placebo plus R-B). Copanlisib/placebo were administered with R-B (days 1, 8, and 15 of each 28-day cycle) for ≤6 cycles and as monotherapy from cycle 7 up to 12 months. The primary study end point was PFS. Median exposure was 8.5 months (0.2-12.9) for copanlisib plus R-B and 11.4 months (0.1-12.6) for placebo plus R-B. Median PFS was 32.9 months (95% confidence interval [CI], 24.4-38.6) for copanlisib plus R-B and 33.3 months (95% CI, 27.8-42.8) for placebo plus R-B (hazard ratio, 1.13; 95% CI, 0.88-1.44; P = .83). No differences between treatment arms were observed in overall survival (data not yet mature), objective response rate, and duration of response for the overall population or individual histology types. Overall, copanlisib plus R-B was associated with higher rates of serious treatment-emergent adverse events (TEAEs), grade 4 and 5 TEAEs, and treatment discontinuation. A number of serious TEAEs were infections. Overall, copanlisib plus R-B did not provide clinical benefit vs placebo plus R-B and was associated with worse tolerability in patients with relapsed iNHL. This trial was registered at www.ClinicalTrials.gov as #NCT02626455. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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