INTEGRATE: A randomized, phase II, double-blind, placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC): A study by the Australasian Gastrointestinal Trials Group (AGITG)-Final overall and subgroup results.

Background: REG is an oral multi-kinase inhibitor warranting evaluation in AOGC following failure of 1st or 2nd line chemotherapy (CT) where few options exist. Method(s):International (Australia & New Zealand (ANZ), Korea, Canada (NCIC CTG)) phase II RCT with 2:1 randomization to 160 mg REG or matched Placebo (PBO) on days (D) 1-21 each 28 D cycle until disease progression (PD) or prohibitive adverse events. Primary endpoint: progression free survival (PFS). Final analysis used data to December 31, 2014. Result(s):152 patients (pts) enrolled (November 2012 to February 2014) yielding 147 pts evaluable for analysis (97 REG and 50 PBO). M:F (118:29); primary site: OGJ (56), stomach (85); lines of prior CT: 1 (62), 2 (85); ECOG PS 0 (62): 1 (85). Median (med.) treatment wks: 8 (REG) v 4 (PBO). Med. REG dose intensity: 150 mg (130 mg Korea and 160mg ANZ/Can). 27 PBO pts received REG following PD. REG Med. PFS 11.1 wks (95% CI: 7.7 - 13.3) v PBO 3.9 wks (3.7 - 4.0), HR 0.40, p < 0.0001. Med. REG OS 25 wks (95% CI: 18.9-29.6) v PBO 19.4 wks (95% CI: 14.9 - 22.7), HR 0.74, p = 0.11. Pre-specified analyses found REG effect greater in Korea than ANZ/Can (HR 0.12 v 0.61, p = 0.0009) but consistent across age, NLR, primary site, lines of CT, peritoneal metastases (mets) presence, number of met. sites, and VEGF-A (Table). Results comparable for ITT population (n = 152). REG was well tolerated, with expected spectrum of toxicities. Conclusion(s): REG was highly effective in prolonging PFS across a broad range of pts, with a non-significant positive OS trend. Regional differences were found in the magnitude of effect but REG was effective in all regions and subgroups. A phase III trial is merited.