FOLFIRINOX combined to targeted therapy according RAS status for colorectal cancer patients with liver metastases initially non-resectable: A phase II randomized Study—Prodige 14 – ACCORD 21 (METHEP-2), a unicancer GI trial.

Abstract

3512 Background: Liver metastases (LM) from colorectal cancer (CRC) are initially resectable in only 10-15% of patients (pts). The conversion to resectability following induction chemotherapy is an important strategy to increase survival. Our study was designed to determine the most appropriate chemotherapy (associated with a targeted therapy) for CRC pts with LM considered as initially unresectable. Methods: This French phase II, multicenter, prospective trial, randomized pts between bi-chemotherapy (BiCT) versus tri-chemotherapy (TriCT). The population was initially stratified by targeted therapy depending on KRAS status and then by RAS status (from 02 Dec 2013 due to the change in cetuximab’s [Cet] marketing authorization): Cet for wt(K)RAS pts and bevacizumab (Bev) for mtRAS pts. The hypothesis was to increase the rate of LM resection (R0-R1) from 50% with BiCT to 70% with TriCT (bilateral α-test 5%; power 90%). Results: 256 patients were randomized in 33 sites from February 2011 till April 2015: 126 BiCT (FOLFIRI [56 pts]; FOLFOX4 [70 pts]) and 130 TriCT (FOLFIRINOX). The resection rate (R0 or R1; CI95%) of the LM was 45.2% [36; 54] for pts treated with BiCT vs 56.9% [48; 66] for TriCT (p = 0.062).The LM resection rate (R0 or R1; CI95%) was 44.7% [35; 55] for pts treated with Bev (mtRAS) vs 55.6% [47; 64] for Cet (wtRAS) (p = 0.087). At the time of data analysis, the median follow-up (CI95%) was 22.5 months [19.6;29.5] for the BiCT pts and 23.5 months [19.8; 28.8] for the TriCT pts and at analysis 78 patients had died. The median overall survival (OS) is significantly different (p = 0.048): in the TriCT Arm the median OS was not reached and is 36 months [23.5;40.6] in the BiCT Arm. The severe toxicity rate was 37.6% for BiCT vs 41.7% for TriCT (p = 0.503). 38 BiCT pts and 34 TriCT pts had surgical complications, with two deaths in each arm. Conclusions: First line FOLFIRINOX chemotherapy, in association with a targeted therapy, showed a higher rate of LM R0/R1 resections than standard BiCT (FOLFIRI or FOLFOX4) combined with the same targeted therapy, with a statistically significant difference in terms of OS. Clinical trial information: 2009-012813-22.