TRICC-C: Nintedanib vs. placebo in patients receiving mFOLFOX6 for metastatic, chemorefractory colorectal cancer: Final results from the randomized phase II trial of the AIO

Abstract

Background: Anti-VEGF agents in combination with chemotherapy improve PFS of patients with mCRC in the 1st- and 2nd-line-setting. During anti-VEGF treatment tumour angiogenesis is driven by other factors but VEGF. Nintedanib is a triple angiokinase inhibitor of human VEGFR-1-3, FGFR-1/-3 and PDGFR-a/-b thereby additionally targets angiogenic escape mechanisms upon resistance to anti-VEGF treatment. The TRICC-C trial evaluates the combination of mFOLFOX6 plus Nintedanib. Final results of the randomized phase II trial are presented. Methods: Patients with mCRC having received one line of non-oxaliplatin containing palliative chemotherapy, with an ECOG-PS of 0 or 1 were randomized 1:1 in a doubleblind design to receive: mFOLFOX6 plus Nintedanib (2 x 200 mg p.o./d, d1-d14) or placebo, respectively, repeated every 14 days. Primary endpoint was PFS. Secondary endpoints were ORR, OS and safety. Patients who received at least one dose of trial medication were included in the efficacy and safety analyses. Results: From12/2012 to 5/2016 53 patients (scheduled n=180) were randomized. The trial was terminated prematurely due to slow accrual. Compared tomFOLFOX6 plus placebo (F+P), the combination ofmFOLFOX6 plusNintedanib (F+N) improvedmPFS (F+P: 4.6 vs F+N: 8.1mo.;HR 0.65; 95%CI 0.32-1.30; p=0.2156),mOS (F+P: 9.9 vs. F+N: 17.1mo.;HR1.03, 95% CI 0.48-2.23; p=0.9387) andDCR (F+P: 50 vs. F+N: 66,7%; p=0.2709). ORR was comparable in both arms (F+N: 3.8 vs. F+P: 3.7%). Toxicity was low tomoderate withoutmajor differences between both arms exceptG 3/4 neutropenia (F+N: 19%, F+P: 12%) andGI disorders (F+N: 23%, F+P: 15%). Conclusions: Final results suggest a PFS, OS and DCR benefit for mFOLFOX6 + Nintedanib vs. mFOLFOX6+placebo in the 2nd-line therapy of mCRC. Due to the premature termination of the trial there was no statistical significance demonstrable. Showing no clinically significant PFS-benefit in the 1st-line situation (mFOLFOX6 plus Nintedanib/Bevacizumab, Ann Oncol. 2015) or the last line as single agent, respectively (ESMO 2016) the TRICC-C results suggests that Nintedanib could be an interesting therapeutic option for the 2nd-line situation in combination with mFOLFOX6.