A new drug combination extends by 46% the time that liver cancer remains stable, according to an international clinical trial led by the Hospital Clínic of Barcelona and presented yesterday in the medical journal The Lancet. The results represent the first advancement since 2002 for patients with inoperable tumors but no metastasis, who account for between 25% and 30% of all liver cancer cases.
“Our data are sufficient to change the clinical treatment guidelines for liver cancer,” states Josep M. Llovet, an Icrea researcher at the Idibaps institute of the Hospital Clínic and coordinator of the study. “For some patients, this drug combination can achieve long-term survival.”
The new strategy involves combining an immunotherapy drug (pembrolizumab) with an anti-angiogenic drug, which prevents the tumor from forming blood vessels (lenvatinib). This prevents the cancer from obtaining nutrients to grow and helps the immune system to better attack it.
The new treatment extends by 46% the time that liver cancer remains stable
This combination of drugs is added to the standard treatment, called transarterial chemoembolization (or TACE for short), which involves administering chemotherapy directly into an artery in the liver and blocking the artery to cut off the blood supply to the tumor.
“We have been searching for ways to improve standard treatment for twenty years. Twelve clinical trials have been conducted, and all have been negative. This is the first time we have shown an improvement,” points out Josep M. Llovet.
In the clinical trial, which involved 137 hospitals from 33 countries, half of the patients received the standard treatment (TACE only) and the other half received the new treatment (TACE plus pembrolizumab plus lenvatinib).
“For some patients, this combination of drugs can achieve long-term survivals,” says Josep M. Llovet
Participants had intermediate-stage liver cancer, which means the cancer had already spread within the liver but had not yet spread to other organs. This is the group of patients for whom TACE is the standard treatment.
For patients diagnosed at an early stage, there are other options such as tumor removal through surgery or undergoing a transplant. For patients at an advanced stage, systemic pharmacological treatments are administered, rather than local treatments in the liver such as TACE.
Nearly 2,000 people a year in Spain and 250,000 worldwide are diagnosed with intermediate-stage liver cancer. These are patients in whom the disease is usually already too advanced to be cured, and the goal of treatment is to achieve the longest possible survival with the highest quality of life.
According to the results presented in The Lancet, the median time that cancer remains stable, without progressing, increases from 10 months with standard treatment to 14.6 months with the new drug combination, a 46% increase.
The median time means that in half of the patients, cancer has progressed, and in the other half, it has not. Therefore, in half of those receiving the new treatment, cancer remains stable for more than 14.6 months.
Since this new treatment incorporates immunotherapy, “we have hope of achieving very long-term survivals in some patients, and even cure in a small percentage, as it happens in other types of tumors treated with immunotherapy,” stated Llovet.
Additionally, the percentage of patients who respond to the treatment is higher with the new drug combination (72%) than with the standard therapy (50%).
The Lancet has presented the preliminary results of the clinical trial, which has not yet concluded. The patients, with an average age of 66 at the start of the treatment, have been followed for a median of 26 months.
Josep M. Llovet, a world reference in liver cancer
Josep M. Llovet is the world's most cited researcher in the field of liver cancer and is part of the top 1% of most cited scientists worldwide across all disciplines, according to data from the consultancy Clarivate Analytics. Among his main contributions is the definition of the different subtypes of liver cancer based on their molecular and immune profile, the discovery of therapeutic targets that can be targeted with drugs, and the clinical development of new therapies such as sorafenib, ramucirumab, and TACE, among others. His work has been cited over 110,000 times in the scientific literature. In addition to being an ICREA researcher at the IDIBAPS institute of the Hospital Clínic, he is a professor at the Universitat de Barcelona and director of the liver cancer program at the Mount Sinai Hospital in New York.
