Phase 3 REFLECT Trial Analysis at ESMO GI 2024 on LENVIMA® Efficacy in Unresectable Hepatocellular Carcinoma

Eisai has presented findings from a new post-hoc analysis of the Phase 3 REFLECT trial at the 2024 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress in Munich. The study focused on the efficacy of LENVIMA® (lenvatinib) as a first-line systemic therapy for patients with unresectable hepatocellular carcinoma (uHCC). Key findings indicated that patients achieving a near-complete response (near-CR) had a similar median overall survival (OS) to those who achieved a complete response (CR).

The analysis included 194 of the 478 patients who were randomly assigned to receive LENVIMA in the REFLECT trial. These patients had an objective response, evaluated via independent imaging review per mRECIST standards. Among these, 10 patients achieved a CR, while 184 experienced a partial response (PR). Within the PR group, 49 patients had a near-CR with a target lesion reduction (TLR) of 75% or more, 72 had a TLR between 50% and 75%, and 63 had a TLR between 30% and 50%.

The results showed that the median OS was 25.4 months for patients with CR and 23.4 months for those with near-CR. These survival times were higher compared to those with PRs with a TLR between 50% and 75% (19.8 months) and a TLR between 30% and 50% (14.4 months). The survival rates at 12 and 24 months were also assessed, showing that patients with CR and near-CR had significantly better outcomes than those with lower TLRs.

The median duration of response (DOR) for patients with CR was 20.3 months. Patients with near-CR and PR with TLRs between 50% and 75% had similar DORs of 7.7 months and 7.3 months, respectively, while those with TLRs between 30% and 50% had a median DOR of 3.7 months. The study found that 10.2% of patients with near-CR maintained their response for over 18 months, whereas 8.3% of patients with a TLR between 50% and 75% maintained their response beyond 18 months.

Dr. Takashi Owa, Chief Scientific Officer and Senior Vice President of Eisai, noted that the findings from this study are significant as they provide deeper insights into the efficacy of LENVIMA. He emphasized that LENVIMA could significantly extend the lives of patients with uHCC, highlighting its potential as a first-line treatment option.

The REFLECT trial itself was a substantial international study, involving 954 patients from 183 sites across 21 countries. This trial aimed to compare the efficacy and safety of LENVIMA against sorafenib, another treatment option for uHCC. Patients were given either 12 mg or 8 mg of LENVIMA daily, based on their body weight, or 400 mg of sorafenib twice daily. The trial concluded that LENVIMA was non-inferior to sorafenib in terms of overall survival but demonstrated superior results in progression-free survival (PFS), time to progression (TTP), and objective response rate (ORR).

Hepatocellular carcinoma (HCC) remains a significant global health issue, being the most common type of primary liver cancer. Despite advances in treatment, the disease often presents at an advanced stage, leading to poor survival rates. The results from the REFLECT trial and ongoing analysis of LENVIMA provide hope for better management and outcomes for patients with this aggressive cancer.

LENVIMA, approved by the FDA in 2018 for the treatment of uHCC, continues to be a critical component of therapy for several cancers. It works by inhibiting kinase activities that are pivotal in tumor growth and cancer progression. The data presented at ESMO GI 2024 underscores its role in extending survival and improving the quality of life for patients with unresectable hepatocellular carcinoma.