Lenvatinib combined with transarterial chemoembolization as first-line treatment of advanced hepatocellular carcinoma: A phase 3, multicenter, randomized controlled trial.

Abstract

380 Background: LAUNCH is a multicenter, randomized, open-label, parallel-group phase 3 trial, aiming to assess the efficacy and safety of lenvatinib plus TACE compared with lenvatinib alone as first-line therapy in patients with advanced hepatocellular carcinoma (HCC). Methods: Patients with advanced HCC were randomly assigned in a 1:1 ratio to receive either lenvatinib plus TACE (LEN-TACE group) or lenvatinib alone (LEN group). Randomized stratification factors include: Eastern Cooperative Oncology Group performance status score (0 vs. 1), tumor thrombus (presence vs. absence), body weight (<60 vs. ≥60kg) and site. In both Len group and LEN-TACE group, patients received oral lenvatinib after randomization within 3 days. The initial dose is 12 mg/day for patients weighing ≥ 60 kg, and 8 mg/day for patients weighing < 60 kg. TACE was started one day after initial lenvatinib in LEN-TACE group and then performed on-demand according to the condition of the tumor and liver function. The primary endpoint were overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR, the proportion of patients with complete response or partial response according to mRECIST), and adverse events. The deadline for interim analysis of data is September 20, 2021. Results: Overall, 338 patients from 12 hospital in China were randomly assigned to receive either lenvatinib plus TACE (n = 170) or lenvatinib (n = 168). The median follow-up duration was 18.4 months (95% confidence interval [CI] 13.7-23.1 months) in the LEN-TACE group and 17.0 months (95% CI 14.2-19.8 months) in the LEN group. The median OS was 17.8 months (95% CI 16.1–19.5) for the lenvatinib-TACE group and 11.5 months (95% CI 10.3–12.7) for the lenvatinib group (stratified hazard ratio [HR] for death = 0.45, 95% CI 0.33–0.61, P<0.001). The median PFS was significantly longer in the LEN-TACE group than in the LEN group (10.6 vs. 6.4 months, HR[hazard ratio]=0.43, P<0.001). Lenvatinib plus TACE improved ORR compared to lenvatinib alone (54.1% vs. 25.0, P<0.001). The following grade 3–4 AEs were more frequently in the lenvatinib-TACE group than in the lenvatinib group: ALT increased (30 [17.6%] vs. 2 [1.2%], P<0.001), AST increased (39 [22.9%] vs. 3 [1.8%], P<0.001), hyperbilirubinemia (16 [9.4%] vs. 5 [3.0%], P=0.014). Conclusions: In conclusion, this trial showed that the combination of lenvatinib plus TACE can improve clinical outcomes and may be the new first-line treatment for patients with advanced hepatocellular carcinoma. Clinical trial information: NCT03905967.