Van Cutsem, E; Yoshino, T; Lenz, H J; Lonardi, S; Falcone, A; Limon, M L; Saunders, M; Sobrero, A; Park, Y S; Ferreiro, R; Hong, Y S; Tomasek, J; Taniguchi, H; Ciardiello, F; Stoehr, J; Oum'Hamed, Z; Vlassak, S; Studeny, M; Argiles, G
Annals of oncology : official journal of the European Society for Medical Oncology
2018Sep ; 29 ( 9 ) :1955-1963.
PMID : 30010751
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Van Cutsem, E - Division of Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium.
Yoshino, T - 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, S - Medical Oncology Unit 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto - IRCCS, Padua.
Falcone, A - Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Limon, M L - Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain.
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 - Department of Clinical Oncology, Ramon y Cajal Hospital, Madrid, Spain.
Hong, Y S - Department of Oncology, Asan Medical Center, Seoul, South Korea.
Tomasek, J - Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Taniguchi, H - Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Ciardiello, F - Oncologia Medica, Seconda Universita 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 - Medical Oncology Department, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, CIBERONC, Barcelona, Spain.
ABSTRACT
BACKGROUND: 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. PATIENTS AND
METHODS: 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.
RESULTS: 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?
CONCLUSIONS: 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. CLINICALTRIALS.GOV NUMBER: NCT02149108 (LUME-Colon 1).
chemorefractory metastatic colorectal cancer, angiogenesis inhibition, nintedanib
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