Combination treatment for liver cancer significantly improves progression-free survival in global trial

Researchers at Mount Sinai have made a breakthrough in treating a type of liver cancer called hepatocellular carcinoma (HCC). This research, led by Josep M. Llovet, MD, Ph.D., Professor of Medicine (Liver Diseases) at the Icahn School of Medicine at Mount Sinai, tested a combination of treatments that could help patients live longer without their cancer getting worse.

Their phase 3 study, titled “LEAP-012: Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma,” was published today in The Lancet.

Liver cancer is a serious and deadly cancer. In 2023, liver cancer was the fourth most common cause of death globally, accounting for more than 800,000 deaths annually. Hepatocellular carcinoma represents approximately 90% of primary liver cancers. This cancer is most commonly found in people living with chronic viral hepatitis, heavy alcohol use, or metabolic dysfunction-associated steatotic liver disease.

This landmark trial demonstrates that the novel combination of lenvatinib, pembrolizumab, and transarterial chemoembolization (TACE) significantly improves progression-free survival compared to TACE alone, addressing a critical unmet need in the treatment of intermediate-stage HCC.

“For over 20 years, TACE has been the standard treatment for intermediate-stage HCC, but its efficacy has been limited,” said Dr. Llovet, who is Director of Mount Sinai’s Liver Cancer Program and a member of The Tisch Cancer Institute, Mount Sinai’s National Cancer Institute-designated clinical cancer center.

“Our study is the first to show a statistically significant improvement in progression-free survival when combining TACE with systemic therapies, paving the way for a potential new standard of care.”

This combination therapy extended the time patients lived without disease progression compared to TACE alone. Additionally, a trend towards improved overall survival was observed, with longer follow-up planned to confirm these results.

“This approach represents a significant step forward in treating the 25% of liver cancer patients classified in the intermediate stage,” said Dr. Llovet.

“For clinicians, this study introduces a groundbreaking approach to managing intermediate-stage HCC by integrating immunotherapy and targeted therapies with established local treatments. For patients, it offers hope for improved disease control and potentially extended survival compared to current standards.”

Future research will focus on evaluating overall survival and exploring the combination’s efficacy in other liver cancer stages and patient populations.

Researchers at Mount Sinai have made a breakthrough in treating a type of liver cancer called hepatocellular carcinoma (HCC). This research, led by Josep M. Llovet, MD, Ph.D., Professor of Medicine (Liver Diseases) at the Icahn School of Medicine at Mount Sinai, tested a combination of treatments that could help patients live longer without their cancer getting worse.

Their phase 3 study, titled “LEAP-012: Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma,” was published today in The Lancet.

Liver cancer is a serious and deadly cancer. In 2023, liver cancer was the fourth most common cause of death globally, accounting for more than 800,000 deaths annually. Hepatocellular carcinoma represents approximately 90% of primary liver cancers. This cancer is most commonly found in people living with chronic viral hepatitis, heavy alcohol use, or metabolic dysfunction-associated steatotic liver disease.

This landmark trial demonstrates that the novel combination of lenvatinib, pembrolizumab, and transarterial chemoembolization (TACE) significantly improves progression-free survival compared to TACE alone, addressing a critical unmet need in the treatment of intermediate-stage HCC.

“For over 20 years, TACE has been the standard treatment for intermediate-stage HCC, but its efficacy has been limited,” said Dr. Llovet, who is Director of Mount Sinai’s Liver Cancer Program and a member of The Tisch Cancer Institute, Mount Sinai’s National Cancer Institute-designated clinical cancer center.

“Our study is the first to show a statistically significant improvement in progression-free survival when combining TACE with systemic therapies, paving the way for a potential new standard of care.”

This combination therapy extended the time patients lived without disease progression compared to TACE alone. Additionally, a trend towards improved overall survival was observed, with longer follow-up planned to confirm these results.

“This approach represents a significant step forward in treating the 25% of liver cancer patients classified in the intermediate stage,” said Dr. Llovet.

“For clinicians, this study introduces a groundbreaking approach to managing intermediate-stage HCC by integrating immunotherapy and targeted therapies with established local treatments. For patients, it offers hope for improved disease control and potentially extended survival compared to current standards.”

Future research will focus on evaluating overall survival and exploring the combination’s efficacy in other liver cancer stages and patient populations.