Lenvatinib Combined With Transarterial Chemoembolization as First-Line Treatment for Advanced Hepatocellular Carcinoma: A Phase III, Randomized Clinical Trial (LAUNCH)

Abstract

PURPOSE Lenvatinib (LEN) is a first-line therapy for patients with advanced hepatocellular carcinoma (HCC); however, it has shown modest survival benefits. Therefore, we aimed to compare clinical outcomes of LEN combined with transarterial chemoembolization (LEN-TACE) versus LEN monotherapy in patients with advanced HCC. MATERIALS AND METHODS This was a multicenter, randomized, open-label, parallel group, phase III trial. Patients with primary treatment-naive or initial recurrent advanced HCC after surgery were randomly assigned (1:1) to receive LEN plus on-demand TACE (LEN-TACE) or LEN monotherapy. LEN was initiated within 3 days after random assignment (initial dose: 12 mg once daily for patients ≥ 60 kg; 8 mg once daily for patients < 60 kg). TACE was initiated one day after LEN initiation. The primary end point was overall survival (OS). RESULTS Between June 2019 and July 2021, a total of 338 patients underwent random assignment at 12 centers in China: 170 to LEN-TACE and 168 to LEN. At a prespecified event-driven interim analysis after a median follow-up of 17.0 months, the median OS was significantly longer in the LEN-TACE group (17.8 v 11.5 months; hazard ratio, 0.45; P < .001). The median progression-free survival was 10.6 months in the LEN-TACE group and 6.4 months in the LEN group (hazard ratio, 0.43; P < .001). Patients in the LEN-TACE group had a higher objective response rate according to the modified RECIST (54.1% v 25.0%, P < .001). Multivariable analysis revealed that portal vein tumor thrombus and treatment allocation were independent risk factors for OS. CONCLUSION The addition of TACE to LEN improves clinical outcomes and is a potential first-line treatment for patients with advanced HCC.

Real-world efficacy and prognostic factors of lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma patients

“…Moreover, we found that combination locoregional therapy was an independent factor for both better PFS and OS. This result was consistent with the results of previous studies that found that adding locoregional therapy to a lenvatinib plus a PD-1 inhibitor or lenvatinib monotherapy therapeutic regimen could lead to a high response and long survival [9,[35][36][37][38][39].…”

“…Most cases are unresectable HCC (uHCC) [1,2]. Patients with uHCC exhibit a median overall survival (OS) of only 11.8-21.2 months for systematic therapy in phase III studies [3][4][5][6][7][8][9][10] and real-world studies [11][12][13][14].…”

Role of Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma

“…Table 2 shows reported outcomes of RCTs for TACE in the treatment of HCC. [13][14][15][16][28][29][30][31][32][33][34][35][36][37][38][39][40]…”

The economics of advanced and unresectable hepatocellular carcinoma

“…However, making a binary therapeutic choice in a cancer as complex as HCC is often neither feasible nor efficacious. Combinatorial treatments, such as levatinib plus transarterial chemoembolization, have been shown in the recently published LAUNCH trial (http://clinicaltrials.gov identifier NCT03905967) to provide a significant survival benefit, further expanding the options available to patients and clinicians 7 . In addition, HCC outcomes are defined by the competing mortality risk conferred by advanced cirrhosis, a group that is excluded in clinical trials.…”

“…Combinatorial treatments, such as levatinib plus transarterial chemoembolization, have been shown in the recently published LAUNCH trial (Clini calTr ials.gov identifier NCT03905967) to provide a significant survival benefit, further expanding the options available to patients and clinicians. 7 In addition, HCC outcomes are defined by the competing mortality risk conferred by advanced cirrhosis, a group that is excluded in clinical trials. In practice, it is necessary to tailor therapy for advanced HCC based not just on cost effectiveness but also on patient characteristics, payor mix, societal expectations, and institutional expertise.…”