Eisai has announced results from the REFLECT study (Study 304), a phase 3 trial evaluating lenvatinib (marketed as Lenvima), the company's multiple receptor tyrosine kinase inhibitor (including fibroblast growth factor receptors [FGFR] 1 – 4), for the first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC). In the trial, lenvatinib demonstrated non-inferiority in overall survival (OS), the primary endpoint of the study, and also demonstrated statistically significant and clinically meaningful improvements on the secondary endpoints of progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR) when compared to sorafenib. The date will be presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

"Unresectable HCC is an extremely difficult-to-treat disease and we have seen no advancements in recent years for first-line systemic treatment, with sorafenib being the only FDA approved systemic therapy in this setting," said Richard Finn, MD, associate professor of Medicine at the Geffen School of Medicine at UCLA and a member of UCLA's Jonsson Comprehensive Cancer Center, and investigator of the study. "Based on the activity of lenvatinib demonstrated across all efficacy endpoints in the REFLECT study, I was very pleased to have been involved in this trial and look forward to continuing research to help patients with advanced liver cancer."

"As patients with unresectable HCC are often symptomatic and face a poor prognosis, improving the rate of patients who respond to treatment is an important step forward for the liver cancer community," said Ari Baron, MD, chief of the Division of Hematology Oncology at California Pacific Medical Center and investigator of the study. "Based on the ORR demonstrated in this trial and the overall efficacy seen in patients treated with lenvatinib as compared to sorafenib, I'm delighted to see this move forward."

The median OS for patients treated with lenvatinib was 13.6 months compared to 12.3 months for sorafenib (HR: 0.92; 95% CI: 0.79 – 1.06). Median PFS was 7.4 months with lenvatinib with a median TTP of 8.9 months compared to median PFS of 3.7 months (HR: 0.66; 95% CI: 0.57 – 0.77; p<0.00001) and median TTP of 3.7 months on sorafenib (HR 0.63; 95% CI; 0.53 – 0.73; p<0.00001). In addition, lenvatinib demonstrated significantly higher ORR (24%) compared to sorafenib (9%) (odds ratio: 3.13; 95% CI: 2.15-4.56; p<0.00001). Endpoints were evaluated using mRECIST and determined by investigator assessment. Independent review is currently underway.

In this study, the most common treatment-emergent adverse events (TEAEs) observed in the lenvatinib arm were hypertension, diarrhea, decreased appetite, decreased weight, and fatigue. Nine percent of patients treated with lenvatinib and 7% of patients treated with sorafenib discontinued treatment due to treatment-related adverse events. Forty-three percent of patients treated with lenvatinib and 30% of patients who received sorafenib experienced serious TEAEs.

"As a company that works tirelessly to serve patients with difficult-to-treat cancers, Eisai is excited by the potential of the results seen with lenvatinib in Study 304 to provide improved outcomes for patients with unresectable HCC, who are in need of additional treatment options," said Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai. "Based on these data, Eisai plans to submit regulatory applications for lenvatinib for the potential first-line treatment of patients with unresectable HCC and we look forward to working closely with the FDA and other regulatory bodies worldwide."

This release discusses investigational uses for an FDA-approved product. It is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such FDA-approved product will gain FDA approval.