Multicenter Phase II Trial of Lenvatinib plus Hepatic Intra-Arterial Infusion Chemotherapy with Cisplatin for Advanced Hepatocellular Carcinoma: LEOPARD

<b><i>Introduction:</i></b> Hepatic arterial infusion chemotherapy (HAIC) with cisplatin and lenvatinib exhibits strong antitumor effects against advanced hepatocellular carcinoma (HCC). Higher antitumor activity is expected for the combination treatment. The aim of this trial was to evaluate the efficacy and safety of lenvatinib in combination with HAIC using cisplatin in patients with advanced HCC. <b><i>Methods:</i></b> In this multicenter, open-labeled, single-arm, phase II trial, patients with advanced HCC categorized as Child-Pugh class A with no prior history of systemic therapy were enrolled. Patients received lenvatinib plus HAIC with cisplatin (lenvatinib: 12 mg once daily for patients ≥60 kg, 8 mg once daily for patients &lt;60 kg; HAIC with cisplatin: 65 mg/m², day 1, every 4–6 weeks, maximum of six cycles). The primary endpoint was the objective response rate (ORR) assessed using modified RECIST by the Independent Review Committee. The secondary endpoints were the ORR assessed using RECIST v1.1, progression-free survival, overall survival, and frequency of adverse events associated with the treatment. <b><i>Results:</i></b> A total of 36 patients were enrolled between September 2018 and March 2020. In the 34 evaluable patients, the ORR assessed by the Independent Review Committee using modified RECIST and RECIST v1.1 were 64.7% (95% confidence interval [CI]: 46.5–80.3%) and 45.7% (95% CI: 28.8–63.4%), respectively. The median progression-free survival and overall survival were 6.3 months (95% CI: 5.1–7.9 months) and 17.2 months (95% CI: 10.9 – not available, months), respectively. The main grade 3–4 adverse events were increased aspartate aminotransferase (34%), leukopenia (22%), increased alanine aminotransferase (19%), and hypertension (11%). <b><i>Conclusion:</i></b> Lenvatinib plus HAIC with cisplatin yielded a favorable ORR and overall survival and was well tolerated in patients with advanced HCC. Further evaluation of this regimen in a phase III trial is warranted.