Eisai Highlights Long-Term Efficacy of Lenvima in Advanced HCC Treatment

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: How do the LEAP-002 findings influence the current treatment landscape for first-line unresectable HCC?

Corina Dutcus: As I mentioned earlier, the consistent efficacy and safety profile of Lenvima can give healthcare professionals confidence when making treatment decisions for their patients. We’ve seen this reaffirmed at ASCO and in numerous publications.

Long-term follow-up data—especially from a Phase III trial such as LEAP-002—are particularly important. They help build trust in the treatment arms by showing whether the outcomes observed early on are maintained over time. The LEAP-002 long-term results offer valuable insights that can support treatment strategies tailored to individual patient characteristics and preferences. That’s a key takeaway from this presentation.

Looking ahead, our research portfolio continues to evolve. For example, we have the Phase III LEAP-012 study, which focuses on earlier-stage, intermediate unresectable hepatocellular carcinoma. We presented initial data from this trial last year at ESMO. This study evaluates Lenvima plus Keytruda in combination with TACE (transarterial chemoembolization) versus TACE alone.

We found that the combination reduced the risk of disease progression or death by 34%. While overall survival data remains immature, we’re eager to present an update on this study in the future.

Full Interview Summary: The LEAP-002 study was a Phase III trial comparing lenvatinib plus Keytruda) versus lenvatinib 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.