Premium
Nintedanib plus mFOLFOX6 as second‐line treatment of metastatic, chemorefractory colorectal cancer: The randomised, placebo‐controlled, phase II TRICC‐C study ( AIO‐KRK ‐0111)
Author(s) -
Ettrich Thomas J.,
Perkhofer Lukas,
Decker Thomas,
Hofheinz RalfDieter,
Heinemann Volker,
Hoffmann Thomas,
Hebart Holger F.,
Herrmann Thomas,
Hannig Carla V.,
BüchnerSteudel Petra,
Güthle Melanie,
Hermann Patrick C.,
Berger Andreas W.,
Seufferlein Thomas
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33296
Subject(s) - medicine , folinic acid , oxaliplatin , nintedanib , clinical endpoint , colorectal cancer , gastroenterology , fluorouracil , placebo , phases of clinical research , progression free survival , oncology , chemotherapy , cancer , clinical trial , pathology , lung , idiopathic pulmonary fibrosis , alternative medicine
Nintedanib is a triple angiokinase inhibitor of vascular endothelial growth factor receptor 1‐3, fibroblast growth factor receptor 1‐3 and platelet‐derived growth factor receptor‐a/‐b. Thereby, it targets angiogenic escape mechanisms. The trial TyRosine kinase Inhibitor for the treatment of Chemorefractory Colorectal Cancer (TRICC‐C) trial evaluates the addition of nintedanib to mFOLFOX6 (fluorouracil, folinic acid and oxaliplatin) in patients with metastatic colorectal cancer (mCRC). TRICC‐C is a randomised controlled, double‐blinded, phase II trial in mCRC patients that received a first‐line non‐oxaliplatin containing chemotherapy. Patients received mFOLFOX6 + nintedanib (F + N) (2 × 200 mg p.o./d, d1‐d14) or mFOLFOX6 + placebo (F + P), in a 1:1 ratio. Primary endpoint was median progression free survival (mPFS) and secondary overall response rate (ORR), overall survival (OS) and safety. Fifty‐three patients (27 F + N; 26 F + P) were randomised between 12/2012 and 5/2016 (scheduled n = 180). The trial was terminated prematurely due to slow accrual. The trial did not reach its primary endpoint but mPFS, median overall survival (mOS) and disease control rate (DCR) were numerically higher in the F + N arm compared to the F + P arm; however, the difference was not significant (mPFS: F + P: 4.6 months vs F + N: 8.1 months; HR 0.65; 95% CI 0.32‐1.30; P = .2156; mOS: F + P: 9.9 months vs F + N: 17.1 months; HR 1.03, 95% CI 0.48‐2.23; P = .9387; DCR: F + P: 50% vs F + N: 66,7%; P = .2709). Toxicity was moderate and only different for neutropenia (F + P: 11.5%, F + N: 19.2%) and gastrointestinal disorders (F + P: 65.4%, F + N: 84.6%). Final results show safety and a nonsignificant trend towards improved PFS and DCR for the combination of mFOLFOX6 + nintedanib in the second‐line therapy of mCRC.