Efficacy and safety of second-line regorafenib after sorafenib or lenvatinib first line in patients with unresectable hepatocellular carcinoma: A real-world study.

e16125 Background: To explore the safety, efficacy and long-term prognosis of patients with unresectable hepatocellular carcinoma (HCC) treated with regorafenib after failure of first-line treatment. Methods: This retrospective single center study included 50 unresectable HCC patients who received regorafenib as a second line treatment in our hospital. Based on the difference of first-line targeted drugs, the 50 patients were divided into sorafenib group (n = 22) and lenvatinib group (n = 28). The adverse events, efficacy and long-term prognosis of sorafenib or lenvatinib followed by regorafenib were analyzed. Results: The median age of the 50 patients was 54.5 years. The patients had the following clinical characteristics: ECOG score 0-1, HbsAg positive, cirrhosis, BCLC stage B/C in 95.5%, 95.5%, 90.9% and 90.9% of all patients respectively. The baseline clinical characteristics between the sorafenib and lenvatinib groups were not statistically different (all p > 0.05), except for age and total bilirubin which were in favour of lenvatinib group. Regorafenib was administered oral 160 mg once daily during weeks 1–3 of each 4-week cycle. For 50 HCC patients, the incidence rate of adverse events after accepting regorafenib was 68%. The incidence rate of grade I/II and III/IV adverse events was 60% and 24%, respectively. According to the standards of RECIST 1.1 and mRSCIST, objective response rate (ORR) and disease control rate (DCR) after receiving regorafenib were 14.0%, 62.0% and 22.0%, 60.0%, respectively. There was no significant difference in incidence of all adverse events and grade III/IV adverse events, ORR and DCR between the two groups ( p > 0.05). In terms of long-term prognosis, total overall survival (TOS) and regorafenib overall survival (ROS) in sorafenib group and lenvatinib group were 23.0 months (95% confidence interval [CI]: 15.1-30.9) vs. 29.7 months (95CI: 21.4-38.1), and 11.7 months (95CI: 7.1-16.3) vs. 15.9 months (95CI: 8.3-23.5). The difference was statistically significant ( p= 0.041 and P = 0.045). The regorafenib progression-free survival (RPFS) was 5.6 months (95CI: 1.9-9.2) vs. 8.0 months (95CI: 5.1-10.9) in sorafenib group and lenvatinib group, respectively. The difference was not statistically significant ( P = 0.380). Conclusions: The data suggest that regorafenib is an effective drug for second-line treatment of HCC, with an acceptable toxicity level, an ORR of 14%-22% and a DCR of 62%-60%. Both TOS and ROS in lenvatinib group are better than those in sorafenib group. The possible mechanisms was that EGFR activation limits the response of HCC cells to lenvatinib. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after the disease progresses.