Feasibility and Tolerability of Lenvatinib, Plus PD-1 Blockades for Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study.

Objective: Lenvatinib was the standard first-line therapy for patients with unresectable HCC. PD-1 blockades demonstrated promising efficacy for patients with previously-treated HCC. Therefore, this study was to investigate the feasibility and tolerability of lenvatinib plus PD-1 blockades for patients with unresectable HCC retrospectively. Methods: A total of 37 patients with unresectable HCC who received lenvatinib plus PD-1 blockades in first-line setting were included in this study retrospectively. Efficacy of the patients was evaluated with the change of target lesion using mRECIST criteria per investigator and all the subjects were followed up regularly. Adverse reactions were collected and documented. Exploratory analysis between prognosis and baseline characteristics was performed using log rank test and multivariate analysis were performed using Cox regression analysis. Results: The best overall response of the 37 patients suggested that complete response was observed in one patient, partial response was noted in 11 patients, stable disease was noted in 16 patients and 9 patients had progressive disease, which yielded an objective response rate (ORR) of 32.4% (95%CI: 18.0-49.8) and a disease control rate (DCR) of 75.7% (95%CI: 58.8-88.2). Furthermore, the median progression-free survival (PFS) of the 37 patients with advanced HCC was 8.3 months (95%CI: 3.34-13.26). And the median overall survival (OS) was 17.8 months (95%CI: 7.19-28.41). In addition, the median duration of response (DoR) in 12 patients with response was 9.6 months (95%CI: 3.03-16.17). Furthermore, adverse reactions that were attributed to the combination administration were detected in 36 patients (97.3%), among whom a total of 22 patients (59.5%) were observed of the grade ≥3 adverse reactions. And the most common adverse reactions were hypertension, fatigue, nausea and vomiting, and hepatotoxicity. Conclusion: Lenvatinib plus PD-1 blockades demonstrated promising anticancer activity and acceptable toxicity for patients with unresectable HCC. And the conclusion should be validated in prospective clinical trials subsequently.