Regional differences in efficacy/safety/biomarkers in a randomised study of axitinib in 2nd line patients (pts) with advanced hepatocellular carcinoma (HCC).

329 Background: A randomised, double-blind phase II study of axitinib plus BSC [AXI] vs placebo plus BSC [PBO] was conducted in HCC pts after failure of one antiangiogenic therapy. Primary outcome was presented at ESMO 2014. No significant differences in overall survival (OS) between two arms were noted overall and in pre-specified subgroup analysis (non-Asian [nA] and Asian [A]). Interestingly, improvements favouring AXI (P < 0.01) were observed in secondary efficacy endpoints and retained among A. Methods: Exploratory efficacy/safety/biomarker analyses were performed by geographic region (nA; A; A subgroups: Japan/Korea [JK] and China/Hong Kong/Taiwan [CHT]) including: OS excluding pts intolerant to prior therapy; relationship between a subset of 26 baseline micro RNAs (miR) and AXI effect. Results: 78 nA pts (76% male, 60% with vascular invasion/extrahepatic spread) and 124 A pts (73JK/51CHT) (86% [84% JK, 90% CHT] male; 86% [82% JK, 92% CHT] with vascular invasion/extrahepatic spread) were randomized. In regional subgroups, OS HR excluding pts intolerant to prior therapy was: nA HR = 0.700 (95% CI 0.373–1.316; p = 0.1318) for AXI (45) vs PBO (16); A HR = 0.653 (95% CI 0.415–1.027; p = 0.0312) for AXI (76) vs PBO (35); JK HR = 0.479 (95% CI 0.250–0.918; p = 0.0118) for AXI (46) vs PBO (17); CHT HR = 0.918 (95% CI 0.480–1.756; p = 0.3954) for AXI (30) vs PBO (18). AXI safety profile was generally similar in regional subgroups. Differences were seen in dose modification pattern: dose reduction or discontinuation due to adverse events in 24% nA / 41% A / 51% JK / 26% CHT or in 39% nA / 22% A / 16% JK / 32% CHT, respectively. miR analysis for OS showed a trend of predictive and/or prognostic effect in overall population (e.g., let-7e-5p); a strong predictive effect of multiple miR (e.g., miR-3648) was seen in A but not in nA. Conclusions: AXI showed favorable OS vs PBO in nA and A, particularly in JK, when pts intolerant to prior therapy were excluded, suggesting that pts who progress on prior therapy are more suitable population for new agent studies in HCC. Appropriate dose modifications may also play a role in treatment duration. Baseline miR signature may have predictive value for AXI OS in A. Clinical trial information: NCT01210495.