Salvage Treatment of Nivolumab and Lenvatinib in Patients with Recurrent Hepatocellular Carcinoma

Background: The clinical efficacy of Lenvatinib (a multi‐kinase inhibitor) and Nivolumab (an immune checkpoint inhibitor) have been shown in the management of hepatocellular carcinoma (HCC). However, real-life experience data of HCC patients receiving the Nivolumab and Lenvatinib combination are scarce, especially those who experienced the first-line or even multi-line treatment. Methods: Recurrent HCC patients (n = 28) treated with Nivolumab plus Lenvatinib as salvage therapy in Hunan Provincial People's Hospital from December 2016 to March 31, 2020, were analyzed. All patients were treated with Nivolumab (3 mg/kg), and Lenvatinib (8 mg/day), and administered every three weeks. Demographics, clinical statistics, and start and end dates of combination therapy were collected and recorded. In addition, progression-free survival (PFS) and OS were calculated from the start of Nivolumab plus Lenvatinib. Treatment outcomes were scored based on the Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. SPSS17.0 software and GraphPad Prism were used for statistical analyses. Results: All the patients had portal vein tumor thrombus (PVTT) who were in Child-Pugh grade A and Barcelona Clinic Liver Cancer (BCLC) stage C. 11 patients (39.3%) were treated with sorafenib only, and 17 patients (60.7%) were treated with at least two lines of multi-target treatment. The disease control rate (CR+PR+SD) was 23/28 (82.1%), with the median overall survival (OS) and median progression-free survival (PFS) of 8.7 months and 5.7 months, respectively. Hyperbilirubinemia was the most common adverse event encountered with these combinations. However, no grade 3 or 4 toxicity was found in all HCC patients. Conclusions: The combination salvage therapy of Nivolumab and Lenvatinib was found effective in HCC patients, and most importantly, the side effects were controllable, and no grade 3 - 4 side effects were observed.