Transcatheter arterial chemoembolization therapy in combination strategy with lenvatinib in patients with unresectable hepatocellular carcinoma (TACTICS-L) in Japan: Final analysis.

417 Background: Treatment options for hepatocellular carcinoma (HCC) include surgical resection, percutaneous ablation therapy, transcatheter arterial chemoembolization (TACE), and liver transplantation, etc., and TACE is indicated for unresectable HCC (uHCC) that is not eligible for curative therapy. Combination therapy with TACE and molecular targeted agents has been reported to have higher antitumor efficacy than respective monotherapies. This study aims to evaluate safety and efficacy of combination of TACE and lenvatinib in uHCC patients. Methods: Phase II, prospective, multicenter, single-arm study was conducted in 19 Japanese sites. Lenvatinib was administered orally once daily for 14 to 21 days prior to TACE at a dose of 12 mg (body weight ≥60 kg) or 8 mg (< 60 kg). The first TACE was performed after a 2-day lenvatinib withdrawal period. This combination therapy was repeated until the time to untreatable progression (TTUP). The primary endpoint was progression-free survival (PFS). Secondary endpoints included TTUP, objective response rate (ORR), overall survival (OS), and safety. Results: Between February 2019 and April 2020, 62 patients were enrolled. Median age was 72.0 years (< 65 years, 13 [21.0%]; ≥65 years, 49 [79.0%]). Number of patients with Child-Pugh score 5 and 6 was 51 (82.3%) and 11 (17.7%); Eastern Cooperative Oncology Group Performance Status 0 and 1 was 59 (95.2%) and 3 (4.8%); and Barcelona Clinic Liver Cancer Stage A and B was 25 (40.3%) and 37 (59.7%). The number of previous TACE procedures was 0 in 35 patients (56.5%) and 1 to 3 in 27 patients (43.5%). The estimated median PFS, OS, and TTUP were more than 2 years. The ORR was 88.7% (90% CI 79.8 – 94.6 with complete response (CR) rate of 66.1%). Treatment emergent adverse events (AEs) occurred in 98.4% of patients, and the most common AEs were hypothyroidism (58.1%), hypertension (53.2%), decreased appetite (50.0%), and fatigue (48.4%). Grade 3 and 4 AEs occurred in 71.0% and 4.8%, and serious AEs occurred in 40.3%. One death not causally related to the protocol treatment was observed. Conclusions: In this final analysis, the combination of TACE and lenvatinib showed promising therapeutic efficacy in patients with uHCC. No new safety signal was observed. Future phase III studies are required to validate this combination therapy. Clinical trial information: jRCTs031180074.