There may be several reasons that HCC cancer of the liver cannot be removed. It may be due to the size of the tumor, or location proximity to major blood vessels, or it may have spread. A new study reported by EISAI US illustrates that Keytruda combo falls short of expectations in overall survival for patients with unresectable hepatocellular carcinoma (HCC) a liver cancer.
HCC is a liver cancer that cannot be removed with surgery because the tumor is too large, is located too close to major blood vessels, or it has spread to other parts of the body.
Merck and Eisai pharmaceutical companies recently issued a news release stating that adding lenvatinib (Lenvima) plus pembrolizumab (Keytruda) to TACE did not significantly increase overall survival benefit for patients compared to TACE alone. TACE is defined as Transarterial Chemoembolization, which is a medical procedure that treats cancer of the liver by sending chemotherapy to the tumor through an artery that concurrently blocks blood from going to the tumor.
The Phase 3 LEAP-012 trial (NCT04246177) that provided the latest reports on the trio confirmed earlier and similar information. The news release stated that there was not a significant achievement in terms of overall survival which was one of the study’s primary end points.
With this information in hand, the developers determined that the likelihood of reaching the threshold at a future date is low and the study was officially closed. Dr. Gregory Lubiniecki, VP of Merck’s clinical development at its Research Laboratories stated the company is grateful to patients and the investigators for their contributions to the study and unwavering commitments to the development of new options to treat HCC which is a challenging and aggressive cancer.
Trial data from LEAP-012 was presented at the 2024 ESMO Congress and published in The Lancet. Reports demonstrated that the combination regimen was a substantial improvement in progression free survival vs TACE alone. However, overall survival, one of the study’s primary endpoints, was not significantly increased.
Four hundred and eighty patients who received TACE with or without lenvatinib were assigned to the phase three trial. The safety profile in both analyses was consistent with previous studies.
Patients who were assigned to the investigational arm received 400 mg of pembrolizumab at 6-week intervals, and lenvatinib at 12 mg for patients who weighed 60 kg or more, or 8 mg for patients with a weight of less than 60 kg. Patients in the placebo arm received intravenous placebo at 6-week intervals, and oral placebo once daily.
TACE was injected by way of the hepatic artery that supplies blood to the liver. Absent any specific discontinuation protocol, patients continued treatment with the exception of pembrolizumab that continued for a period of two years approximating 18 doses.
Primary and Secondary End Points
Primary end points, such as progression free survival came under review in accordance with RECIST v1.1., as well as overall survival.
Secondary end points included response rate, objective duration of response, disease control rate, and time to progression. They are all assessed by BICR per RECIST v1.1 criteria, which is a set of rules used by clinical trials objectively assessing the response of solid tumors and how they respond to cancer therapy.
About Safety Data
Interim analysis from the first safety data found that 98.7% of those treated by the investigational process as opposed to TACE alone showed adverse effects that were attributed to the investigational process.
