Lenvatinib, sintilimab plus transarterial chemoembolization for advanced stage hepatocellular carcinoma: A phase II study

Abstract

Background & AimsOur retrospective study has suggested encouraging outcomes of lenvatinib combined with PD‐1 inhibitor and transarterial chemoembolization (TACE) on advanced hepatocellular carcinoma (HCC). This phase II trial was conducted to prospectively investigate the efficacy and safety of lenvatinib, sintilimab (a PD‐1 inhibitor) plus TACE (Len‐Sin‐TACE) in patients with advanced stage HCC.MethodsThis was a single‐arm phase II trial. Patients with BCLC stage C HCC were recruited. They received lenvatinib (bodyweight ≥60 kg, 12 mg; bodyweight <60 kg, 8 mg) orally once daily, sintilimab (200 mg) intravenously once every 3 weeks, and on demand TACE. The primary endpoint was progression‐free survival (PFS) per mRECIST.ResultsThirty patients were enrolled. The primary endpoint was met with a median PFS of 8.0 (95% confidence interval [CI]: 6.1–9.8) months per mRECIST, which was the same as that per RECIST 1.1. The objective response rate was 60.0% per mRECIST and 30.0% per RECIST 1.1. The disease control rate was 86.7% per mRECIST/RECIST 1.1. The median duration of response was 7.4 (95% CI: 6.6–8.2) months per mRECIST (n = 18) and 4.3 (95% CI: 4.0–4.6) months per RECIST 1.1 (n = 9). The median overall survival was 18.4 (95% CI: 14.5–22.3) months. Treatment‐related adverse events (TRAEs) occurred in 28 patients (93.3%) and grade 3 TRAEs were observed in 12 patients (40.0%). There were no grade 4/5 TRAEs.ConclusionsLen‐Sin‐TACE showed promising antitumour activities with a manageable safety profile in patients with advanced stage HCC. The preliminary results need to be further evaluated with phase III randomized trials.

Clinical benefits of transarterial chemoembolization combined with tyrosine kinase and immune checkpoint inhibitors for unresectable hepatocellular carcinoma

“…A flowchart of the study selection is illustrated in Figure 1 . After excluding ineligible studies, 29 articles[ 17 - 45 ] with 1754 patients were included. Among the included studies, 27 were retrospective studies and 2 were prospective studies.…”

“…A multicenter retrospective matched-cohort study of patients with HCC from 59 hospitals in China found that TACE combination therapy with PD-(L)1 inhibitors and molecular targeted agents significantly improved the median PFS, median OS, and ORR compared with TACE monotherapy[ 16 ]. A single-arm phase II trial based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) revealed that TACE plus lenvatinib and PD-1 inhibitors exhibited a high ORR of 60.0%, disease control rate (DCR) of 86.7%, long median OS of 18.4 months, and median PFS of 8.0 months, with 93.3% adverse events (AEs) of any grade, 40.0% grade 3 TRAEs, and no grade 4/5 TRAEs in patients with advanced HCC[ 17 ]. To date, numerous clinical trials and studies with or without control or intervention measures have explored the benefits of combination therapies of TACE with TKIs and ICIs using different treatment regimens and have achieved encouraging results.…”

Advancements in Immunotherapeutic Treatments for Hepatocellular Carcinoma: Potential of Combination Therapies

“…The tumor spreads extensively at advanced-stage HCC, leading to poor prognosis and limited treatment approaches compared to the early and intermediate stages [78]. Immunotherapy and combination therapy have gained attention as promising options for treating patients with advanced-stage HCC, as chemotherapy, TACE, and RFA have shown limited efficacy [79]. Nivolumab (ICI, anti-PD-1 antibody) was administered to 145 advanced-stage HCC patients who participated in a phase I/II trial at a dose of 3 mg/kg once every 14 days [80].…”