Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1) : a phase III, international, randomized, placebo-controlled study
Van Cutsem, E. (University Hospitals Gasthuisberg (Leuven, Bélgica))
Yoshino, Takayuki (Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan)
Lenz, H. J. (Division of Medical Oncology, Norris Comprehensive Cancer Center, Los Angeles, USA)
Lonardi, Sara (Medical Oncology Unit 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto - IRCCS, Padua)
Falcone, Alfredo (Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy)
Limón, M. L. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Saunders, M. (Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK)
Sobrero, A. (Department of Medical Oncology, Azienda Ospedaliera San Martino, Genoa, Italy)
Park, Y S. (Department of Hematology and Oncology, Samsung Medical Center, Seoul, South Korea)
Ferreiro, R. (Hospital Universitario Ramón y Cajal (Madrid))
Hong, Y S. (Department of Oncology, Asan Medical Center, Seoul, South Korea)
Tomasek, J. (Masaryk Memorial Cancer Institute (Brno, República Txeca))
Taniguchi, H. (Aichi Cancer Center Hospital)
Ciardiello, Fortunato (Oncologia Medica, Seconda Università deli Studi di Napoli, Naples, Italy)
Stoehr, J. (Boehringer Ingelheim, Pharma GmbH & Co. KG, Biberach, Germany)
Oum'Hamed, Z. (Boehringer Ingelheim France S.A.S, Reims, France)
Vlassak, S. (SCS Boehringer Ingelheim Comm.V, Brussels, Belgium)
Studeny, M. (Division of Medicine/Clinical Development Department, Boehringer Ingelheim, Vienna, Austria)
Argiles, G.. (Vall d'Hebron Institut d'Oncologia)
Universitat Autònoma de Barcelona

Data:	2018
Resum:	Angiogenesis is critical to colorectal cancer (CRC) growth and metastasis. Phase I/II studies have demonstrated the efficacy of nintedanib, a triple angiokinase inhibitor, in patients with metastatic CRC. This global, randomized, phase III study investigated the efficacy and safety of nintedanib in patients with refractory CRC after failure of standard therapies. Eligible patients (Eastern Cooperative Oncology Group performance status 0-1, with histologically/cytologically confirmed metastatic/locally advanced CRC adenocarcinoma unamenable to surgery and/or radiotherapy) were randomized 1 : 1 to receive nintedanib (200 mg twice daily) or placebo (twice daily), until disease progression or undue toxicity. Patients were stratified by previous regorafenib, time from onset of metastatic disease to randomization, and region. Co-primary end points were overall survival (OS) and progression-free survival (PFS) by central review. Secondary end points included objective tumor response and disease control by central review. From October 2014 to January 2016, 768 patients were randomized; 765 were treated (nintedanib n = 384; placebo n = 381). Median follow-up was 13. 4 months (interquartile range 11. 1-15. 7). OS was not improved [median OS 6. 4 months with nintedanib versus 6. 0 months with placebo; hazard ratio (HR), 1. 01; 95% confidence interval (CI), 0. 86-1. 19; P = 0. 8659]. There was a significant but modest increase in PFS with nintedanib versus placebo (median PFS 1. 5 versus 1. 4 months, respectively; HR 0. 58; 95% CI 0. 49-0. 69; P < 0. 0001). There were no complete or partial responses. Adverse events (AEs) occurred in 97% of 384 nintedanib-treated patients and 93% of 381 placebo-treated patients. The most frequent grade ≥3 AEs were liver-related AEs (nintedanib 16%; placebo 8%) and fatigue (nintedanib 9%; placebo 6%). The study failed to meet both co-primary end points. Nintedanib did not improve OS and was associated with a significant but modest increase in PFS versus placebo. Nintedanib was well tolerated. NCT02149108 (LUME-Colon 1).
Nota:	Altres ajuts: Funding for this study was provided by Boehringer Ingelheim. No grant number applied.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Chemorefractory metastatic colorectal cancer ; Angiogenesis inhibition ; Nintedanib
Publicat a:	Annals of oncology, Vol. 29 (july 2018) , p. 1955-1963, ISSN 1569-8041

DOI: 10.1093/annonc/mdy241
PMID: 30010751

9 p, 325.6 KB

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