Key Takeaways of the Survival Outcomes From the LEAP-002 Trial for HCC

Richard S. Finn, MD, discusses key takeaways of the LEAP-002 trial of frontline pembrolizumab and lenvatinib for hepatocellular carcinoma.

Richard S. Finn, MD, professor of medicine in the division of hematology/oncology, department of medicine at the Geffen School of Medicine at UCLA, discusses key takeaways of the LEAP-002 trial (NCT03713593) of frontline pembrolizumab (Keytruda) and lenvatinib (Lenvima) for hepatocellular carcinoma (HCC).

Results of the phase 3 study presented at the 2022 European Society for Medical Oncology Congress showed a 21-month median overall survival (OS) for the pembrolizumab/lenvatinib combination; however, the comparator arm of lenvatinib alone had a median OS of 19 months, with the difference being insufficient to show survival benefit of the combination. Finn notes that lenvatinib alone showed an impressive OS, though this was in a population that excluded those with a main portal vein invasion.

According to Finn, the HIMALAYA study (NCT03298451), which recently led to the approval of durvalumab (Imfinzi) plus tremelimumab (Imjudo), had a median OS of around 16 months. Additionally, the IMbrave150 study (NCT03434379) of atezolizumab (Tecentriq) and bevacizumab (Avastin) reached a median OS of over 19 months in a higher-risk population, including main portal vein invasion. Despite not reaching statistically significant survival benefit when combined with pembrolizumab, Finn says the comparator arm’s outcomes indicates that lenvatinib has an important role in HCC.

Pembrolizumab and lenvatinib are also under investigation in the LEAP-012 trial (NCT04246177) in combination with transarterial chemoembolization (TACE) in patients with incurable nonmetastatic HCC, which could show a different role for this combination.


0:08 | A few things we learned from this study: lenvatinib and pembrolizumab are safe. It's active in liver cancer but was not statistically better than lenvatinib alone. What we did learn is that lenvatinib alone is a very active regimen for patients in the frontline setting, giving an OS of 19 months. It's important to note that the 19 months is in a population that did not have a main portal vein invasion.

If we look at other phase 3 studies in that space, [these results] compare to the HIMALAYA study where durvalumab and tremelimumab had a survival of around 16 months. But when the IMbrave150 study of atezolizumab and bevacizumab reports a survival of over 19 months; that is in a higher-risk population, i.e, patients who did have, or included, main portal vein invasion.

0:59 | Lenvatinib is an important option for our patients with advanced liver cancer. It's important to keep that in mind. [This combination] is still being evaluated in another phase 3 study of lenvatinib and pembrolizumab plus TACE for patients with intermediate liver cancer as well. That's a phase 3 study of that combination versus TACE alone.