Lenvatinib/TACE May Be Efficacious, Safe as First-Line Treatment for Advanced HCC

Treatment with transarterial chemoembolization (TACE) and lenvatinib (Lenvima) yielded notable improvements in survival and responses for patients with advanced hepatocellular carcinoma (HCC) and could be a promising first-line treatment option, according to findings from the phase 3 LAUNCH trial presented at the 2022 Gastrointestinal Cancers Symposium.

When assessed by RECIST 1.1 criteria, patients had an objective response rate (ORR) of 45.9% following the TACE regimen vs 20.8% with single agent lenvatinib (P <.001). When analyzed with a modified RECIST criteria, the ORR was 54.1% vs 25.0% in the 2 respective arms (P <.001). Moreover, the experimental arm experienced a median overall survival (OS) of 17.8 months compared with 11.5 months in the lenvatinib arm (HR, 0.45; 95% CI, 0.33-0.61; P <.001). Median progression-free survival (PFS) was 10.6 months and 6.4 months in each arm, respectively (HR, 0.43; 95% CI, 0.34-0.55; P <.001).

“Tumor burden is a major threat to the improvement of lenvatinib. A potential treatment strategy to enhance the efficacy of lenvatinib for advanced HCC is to combine it with a local therapy such as TACE. TACE can reduce tumor burden in a very short time,” according to Zhenwei Ping, MD, PhD, a member of the Department of Medical Oncology at Sun Yat-Sen University, who explained the rationale for the research. He continued, “The combination of these 2 treatments may provide a better choice than lenvatinib alone, but we [did] not have solid data.”

To enroll on the study, patients could not have previously received a prior treatment or have initial recurrent advanced disease following radical resection. Patients needed to have at least 1 measurable lesion of the liver that was 10 cm or less or multiple lesions 10 foci or less with a tumor burden less than 50%. Other eligibility criteria including a Child-Pugh A grade, an ECOG performance status of 1 or less, and adequate blood, liver, and kidney function. Patients were stratified based on ECOG performance status, tumor thrombus, body weight and trial site.

Patients were randomized 1:1 to either the TACE (n = 168) or lenvatinib monotherapy (n = 168) arms. In the experimental cohort, TACE was administered on day 1 following treatment with lenvatinib, which was administered at 8 mg once daily if the patient’s body weight was less than 60 kg or 12 mg if they weighed 60 kg or more.

The study’s primary end point was OS, with key secondary end points including PFS, ORR, time to progression, and quality of life.

Baseline characteristics were balanced between the 2 arms, with a median age of 54 and 56 years in both the TACE and single agent arms, respectively. Most patients were 60 years of age or younger. Additionally, most patients in both arms were male (81.8% vs 78.6%), had hepatitis B (87.1% vs 85.7%), and had an ECOG performance status of 0 (52.4% vs 58.9%).

Additional findings from the study when assessed via RECIST 1.1 criteria included 1 complete responder in each of the treatment arms. Moreover, in the TACE arm, investigators reported a partial response (PR) rate of 45.3%, a stable disease rate of 46.5%, a progressive disease rate of 7.6%, and a disease control rate (DCR) 92.4%. In the monotherapy group, patients had a PR rate of 20.2%, a stable disease rate of 51.8%, a progressive disease rate of 27.4%, and a DCR of 72.6%. When assessed by a modified RECIST criteria, the CR rate was 2.9% vs 0.6%, the PR rate was 51.2% vs 24.4%, the stable disease rate was 40.0% vs 48.2%, the progressive disease rate was 5.9% vs 26.8%, and the DCR was 94.1% vs 73.2% in the TACE and lenvatinib arms, respectively.

The median duration of treatment with lenvatinib was 8.2 months in the experimental group compared with 5.1 months in the control group. In the TACE cohort, 52.9% of patients needed dose reductions, 44.7% needed interruptions, and 8.8% discontinued treatment with lenvatinib compared with 44.6%, 39.9%, and 8.3% of patients in the monotherapy cohort. Patients in the lenvatinib/TACE arm underwent treatment with TACE 560 times, with a median of 3 sessions per patient. The most common reasons for discontinuing treatment with TACE included disease progression, hepatic reaction, disappearance of intratumoral arterial enhancement in lesion, and unacceptable adverse effects (AEs).

Findings from the multivariate analysis indicated the portal vein tumor thrombus (PVTT) and treatment allocation were independent risk factors of OS, and age, PVTT, and treatment allocation were independent risk factors of PFS.

The most significant any grade AEs included abdominal pain (P <.001), nausea (P <.001), fever (P <.001), ascites (P = .004), vomiting (P <.001), alanine transaminase (ALT) increase (P <.001), aspartate aminotransferase (AST) increase (P <.001), hyperbilirubinemia (P = .29), and hypoalbuminemia (P = .001). The most notable grade 3/4 AEs included ALT increase (P <.001), AST increase (P <.001), and hypoalbuminemia (P = .014).

A total of 15.3% of patients in the experimental arm underwent surgery due to tumor downstaging, 2 patients of whom achieved a CR. In comparison, 1.8% of patients in the monotherapy arm underwent surgery, with no patients achieving a CR (P <.001). Most patients underwent treatment with a PD-1 inhibitor or other targeted therapy after discontinuing treatment.

Reference

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. 2022 Gastrointestinal Cancers Symposium; January 20-22, 2022; Virtual. Abstract 380.