Nintedanib plus mFOLFOX6 as second-line treatment of metastatic, chemorefractory colorectal cancer: the randomized, placebo-controlled, phase II TRICC-C study (AIO-KRK-0111).

Nintedanib is a triple angiokinase-inhibitor of VEGF-receptor 1-3, FGF-receptor 1-3 and PDGF-receptor-a/-b. Thereby it targets angiogenic escape mechanisms. The TRICC-C trial evaluates the addition of nintedanib to mFOLFOX6 in patients with mCRC. TRICC-C is a randomized 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 x 200 mg p.o./d, d1-d14) or mFOLFOX6+placebo (F+P), in a 1:1 ratio. Primary endpoint was mPFS and secondary overall response rate (ORR), overall survival (OS) and safety. 53 patients (27 F+N; 26 F+P) were randomized between 12/2012 to 5/2016 (scheduled n=180). The trial was terminated prematurely due to slow accrual. The trial did not reach its primary endpoint but mPFS, 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 mo. vs. F+N: 8.1 mo.; HR 0.65; 95% CI 0.32-1.30; p = 0.2156; mOS: F+P: 9.9 mo. vs. F+N: 17.1 mo.; HR 1.03, 95% CI 0.48-2.23; p = 0.9387; DCR: F+P: 50% vs. F+N: 66,7%; p = 0.2709). 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 non-significant trend towards improved PFS and DCR for the combination of mFOLFOX6+nintedanib in the 2nd-line therapy of mCRC. This article is protected by copyright. All rights reserved.