748PMulticentric prospective study of validation of angiogenesis-related gene polymorphisms in HCC patients treated with sorafenib: Final results of INNOVATE study

Background In two retrospective studies we analyzed endothelial-derived nitric oxide synthase (eNOS) and angiopoietin-2 (ANGPT2) polymorphisms, and patients with eNOS-786CC+TC genotype and ANGPT2rs55633437 GG genotypes had significantly higher median PFS and OS compared to those with other genotypes. On the basis of these preliminary results, our aim was to validate in a prospective study these data in patients with HCC treated with sorafenib (S). Methods The primary outcomes were PFS. 160 total sample size was planned with the aim to confirm a HR of 0.58. Event-time distributions were estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test Results 165 patients were prospectively enrolled in the study between 03/2015 and 06/2018. Median OS was 13.1 months and median PFS was 4.2 months. We confirmed that eNOS-786 CC+CT genotype was significantly associated with a higher median PFS (2.4 vs 5.9 months, HR 0.43, 95% CI 0.26-0.70 p = 0.0007) and OS (15.7 vs 8.6 months, HR 0.38, 95% CI 0.24-0.60 p Conclusions Our Italian multicenter, prospective study met its primary and secondary end points, and we confirmed that eNOS-786 CC+CT genotype may be capable of identifying a subset of HCC patients who have a higher median OS and PFS. For the first time in ten years of sorafenib research our study confirms the prognostic role of a biological marker in a prospective study. Clinical trial identification NCT02786342. Legal entity responsible for the study University of Modena. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.