LEAP-002 Study Shows Five Year Survival Consistency in Unresectable Liver Cancer

In an interview with Pharmaceutical Executive, Corina Dutcus, SVP, oncology global clinical development lead at Eisai, discussed new long-term data from the LEAP-002 trial and the company’s broader efforts in liver and endometrial cancer. The Phase III LEAP-002 study evaluated lenvatinib alone versus in combination with Keytruda (pembrolizumab) in first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). While the primary endpoint was not met, updated follow-up results presented at nearly five years provide new insights into the therapy’s sustained benefit and reinforce its role in HCC care. Dutcus also shared updates on Eisai’s investigational WNT pathway inhibitor, E7386, and its promising early data in endometrial carcinoma, underscoring the company’s commitment to advancing novel treatment strategies in areas of high unmet need.

Pharmaceutical Executive: Could you share the key insights from the long-term follow-up data of the LEAP-002 study comparing lenvatinib plus pembrolizumab versus lenvatinib monotherapy in unresectable hepatocellular carcinoma?

Corina Dutcus: One of the key highlights we presented was the long-term follow-up data from the LEAP-002 study—a Phase III trial in first-line hepatocellular carcinoma (HCC) patients. Participants were randomized to receive either lenvatinib plus pembrolizumab or lenvatinib monotherapy.

Although the study did not meet its primary endpoint in the initial analysis, we continued following patients and, at 59 months—essentially five years—we presented updated safety and efficacy results. This presentation was very well received, not just by the broader oncology community, but especially by the hepatocellular carcinoma community. The data reinforced lenvatinib’s established role as a first-line treatment option for appropriate patients with unresectable HCC.

At nearly five years of follow-up, the median overall survival for the lenvatinib monotherapy arm remained at 19 months, consistent with the primary analysis. This consistency over time was reassuring to both investigators and prescribers, confirming the durability of the treatment effect.

Additionally, the safety profile of lenvatinib remained stable, with no new safety signals or increased rates of adverse events. The same was true for the combination arm with pembrolizumab—no unexpected toxicities or new concerns emerged.

Importantly, hepatocellular carcinoma continues to represent a major unmet need, with incidence rates projected to rise by 50% over the next two decades. This makes it even more critical that we continue our research in this space to deliver meaningful treatment options.

To put things in perspective: at 60 months, the overall survival rate was close to 20% for the lenvatinib plus pembrolizumab arm versus around 10% for lenvatinib alone. Twice as many patients remained in follow-up in the combination arm compared to monotherapy. Grade 3–5 adverse events remained consistent with the primary analysis as well. Altogether, these long-term data reinforce lenvatinib’s established position in first-line treatment for liver cancer, particularly hepatocellular carcinoma.

Full Interview Summary: The LEAP-002 study was a Phase III trial comparing lenvatinib plus Keytruda) versuslenvatinib monotherapy in patients with unresectable hepatocellular carcinoma (HCC) in the first-line setting. Although the primary endpoint was not met, long-term follow-up at 59 months (nearly five years) reaffirmed the efficacy and safety profile of lenvatinib. Median overall survival for lenvatinib monotherapy remained at 19 months, consistent with earlier findings, and no new safety signals emerged. These results strengthen lenvatinib’s role in monotherapy for appropriately selected HCC patients.

Notably, twice as many patients remained in follow-up in the combination arm, and the long-term survival rate was approximately 20% with the combination versus 10% for lenvatinib alone. Adverse events (Grade 3–5) also remained in line with earlier data. Given the projected 50% increase in HCC incidence over the next two decades, these findings are crucial for guiding current treatment strategies and reinforcing physician confidence.

Looking ahead, Eisai is also investigating earlier-stage HCC through theLEAP-012 trial, evaluating lenvatinib and pembrolizumab with TACE (transarterial chemoembolization). Interim results show a 34% reduction in progression or death, though overall survival data remains immature.

In endometrial carcinoma, Eisai is developing E7386, a WNT pathway modulator that inhibits CBP–β-catenin interaction. Early data from a 30-patient expansion cohort combining E7386 with lenvatinib showed a 30% response rate overall, rising to 44% in lenvatinib-naive patients post-chemotherapy and IO. The median duration of response was eight months.

The company has now advanced to a randomized trial comparing two doses of E7386 plus Lenvatinib, versus lenvatinib aloneand standard of care, in the second-line setting. This approach aims to optimize efficacy while minimizing toxicity, addressing ongoing unmet needs in advanced endometrial carcinoma.