KEYTRUDA® + LENVIMA® With Chemoembolization Improves Survival in Unresectable Hepatocellular Carcinoma

Merck and Eisai recently unveiled findings from the first interim analysis of their Phase 3 LEAP-012 trial. This study assessed the efficacy of combining KEYTRUDA (pembrolizumab) and LENVIMA (lenvatinib) with transarterial chemoembolization (TACE) against TACE alone in treating patients with unresectable, non-metastatic hepatocellular carcinoma (HCC). These results were highlighted at the European Society for Medical Oncology (ESMO) Congress 2024.

After a median follow-up period of 25.6 months, the combination of KEYTRUDA and LENVIMA with TACE showed a significant reduction in the risk of disease progression or death by 34% compared to TACE alone, with a hazard ratio of 0.66 and a p-value of 0.0002. Specifically, the median progression-free survival (PFS) for the combination therapy was 14.6 months, in contrast to 10.0 months for TACE alone. Although there was an observed trend towards improved overall survival (OS), this data was not yet mature enough to be deemed statistically significant at this stage of the interim analysis.

Dr. Josep Llovet, from the Icahn School of Medicine at Mount Sinai, emphasized the significance of these findings, noting the pressing need for new therapeutic options in treating HCC, a major cause of cancer-related deaths globally. Dr. Gregory Lubiniecki from Merck echoed this sentiment, highlighting the growing global incidence rates of HCC and the limited advancements in treating unresectable, non-metastatic forms of the disease. He expressed optimism about the potential of this combination therapy to address an unmet need.

The safety profile of the KEYTRUDA plus LENVIMA regimen was consistent with previous studies. However, treatment-related adverse events (TRAEs) were more common in patients receiving the combination therapy compared to those receiving TACE alone. Serious TRAEs were observed in 33.3% of patients on the combination therapy versus 12.4% on TACE alone. Grade 3 or 4 TRAEs occurred in 71.3% of patients on the combination therapy compared to 31.1% for TACE alone, and TRAEs led to death in 1.7% of patients on the combination therapy versus 0.4% on TACE alone.

LENVIMA is approved in over 80 countries for treating unresectable HCC as a monotherapy. KEYTRUDA, on the other hand, is approved in the U.S. and China for HCC patients who have undergone prior systemic therapy. The combination of KEYTRUDA and LENVIMA is also approved in various regions for treating advanced renal cell carcinoma and certain types of advanced endometrial carcinoma. Both companies are actively studying this combination through the LEAP clinical program across multiple tumor types.

The LEAP-012 study is a multicenter, randomized, double-blind Phase 3 trial involving 480 patients. The primary endpoints of the study include PFS and OS, with secondary endpoints encompassing objective response rate, duration of response, disease control rate, and time to progression. The patients were randomized to receive either the combination of KEYTRUDA and LENVIMA with TACE or dual placebo plus TACE.

Liver cancer, particularly HCC, remains a leading cause of cancer-related deaths worldwide. In the U.S., incidence rates have more than tripled since 1980, with death rates doubling during the same period. The five-year relative survival rate for liver cancer in the U.S. is 22%.

KEYTRUDA is an anti-PD-1 therapy that enhances the immune system's ability to detect and combat tumor cells. It is part of the largest immuno-oncology clinical research program, with over 1,600 trials exploring its efficacy across various cancers. LENVIMA, developed by Eisai, is an orally available multiple receptor tyrosine kinase inhibitor that targets several kinases involved in tumor growth and cancer progression.