Although lenvatinib is the most widely used targeted therapy for the treatment of advanced hepatocellular carcinoma (HCC), there is still room to improve its efficacy. The phase III LAUNCH study could demonstrate that the combination of lenvatinib plus transarterial chemoembolisation was safe and effective for patients with advanced HCC and may represent a new first-line treatment option for patients with advanced HCC.
As of 2018, lenvatinib is recommended as a systemic first-line treatment option for patients with advanced hepatocellular carcinoma (HCC). A potential treatment strategy to further enhance the efficacy of lenvatinib is to combine it with local treatments, such as transarterial chemoembolisation (TACE). LAUNCH is a phase III, multicentre, randomised controlled trial to compare the efficacy of lenvatinib plus TACE with lenvatinib monotherapy as the first-line treatment of advanced HCC and to evaluate the efficacy and safety of this combination.
LAUNCH study design
In the LAUNCH study, treatment-naïve patients with advanced HCC were randomly assigned (1:1) to receive either lenvatinib plus TACE (LEN-TACE group) or lenvatinib alone (LEN group). Stratification factors for randomisation included Eastern Cooperative Oncology Group performance status score (0 vs. 1), tumour thrombus (presence vs. absence), body weight (<60 vs. ≥60kg) and site. In both study arms, patients received oral lenvatinib after randomisation within three days. The initial dose was set at 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 the LEN-TACE group and then performed on-demand according to the condition of the tumour and liver function. The primary endpoint of the study was overall survival (OS).
In total, 338 patients from twelve Chinese hospitals were randomly allocated to LEN-TACE (N= 170) or LEN (N= 168). In general, the two groups had balanced baseline characteristics. After a median follow-up of 18.4 months in the LEN-TACE group and 17.0 months in the LEN group, the median OS was 17.8 and 11.5 months, respectively, translating into a 55% reduction in the risk of death with the LEN-TACE combination (HR[95%CI]: 0.45[0.33-0.61], p< 0.001). Furthermore, the median progression-free survival (PFS) was significantly longer in the LEN-TACE group than in the LEN group (10.6 vs. 6.4 months, HR[95%CI]: 0.43[0.34-0.55], p< 0.001). The OS and PFS benefit of LEN-TACE was observed across most of the analysed subgroups. While portal vein tumour thrombus (PVTT) and treatment allocation were independent risk factors for OS, age, PVTT and treatment allocation were independent risk factors for PFS. Lenvatinib plus TACE improved both the objective response rate (54.1% vs. 25.0%, p< 0.001) and the disease control rate (94.1% vs. 73.2%, p< 0.001) compared to lenvatinib alone. The following grade 3–4 AEs were more frequently in the LEN-TACE group than in the lenvatinib group: increased ALT (17.6% vs. 1.2%, p< 0.001), increased AST (22.9% vs. 1.8%, p< 0.001) and hyperbilirubinemia (9.4% vs. 3.0%, p= 0.014). With regard to subsequent treatment after discontinuation, curative surgical resection was conducted for 26 (15.3%) patients in the LEN-TACE group owing to downstaging, and two (1.2%) patients experienced a pathologic complete response. In contrast, only three (1.8%) patients in the LEN group received curative surgery and no patients experienced a pathologic complete response (p< 0.001). Most patients received PD-1 antibody treatment or other targeted therapy after discontinuation. The median duration of lenvatinib treatment was 8.2 months in the LEN-TACE group, and 5.1 months in the LEN group. Furthermore, patients in the LEN-TACE group were treated with a total of 560 times of TACE, and the median TACE session per patient was 3 (range 1-6).
Lenvatinib plus TACE was safe and effective for patients with advanced HCC, demonstrating remarkable improvements in OS, PFS and ORR, as well as acceptable toxicity. Therefore, lenvatinib plus TACE may represent a potential new first-line treatment option for patients with advanced HCC.
Peng Z, Fan W, Zhu B, et al. Lenvatinib combined with transarterial chemoembolization as first-line treatment of advanced hepatocellular carcinoma: A phase 3, multicenter, randomized controlled trial. Presented at ASCO GI 2022; Abstract 380.