Professor Jeon Hong-jae, Bundang CHA Hospital Progression-free survival (PFS), which refers to the period of time that the patient survives because the cancer cells that stopped growing while the anticancer drug administered to the cancer patient is effective and does not grow again, is one of the main indicators for evaluating anticancer drugs. Some people discount the significance of anticancer drugs that cannot prove PFS.
However, with the advent of immunotherapy drugs, there is an increasing number of interpretations that PFS is not an absolute indicator for liver cancer. Regardless of PFS improvement, new drugs are succeeding in extending the survival time (OS) of cancer patients. A representative example is the combined treatment of AstraZeneca‘s ‘Imfinzi’ and ‘Imudo’ for liver cancer.
Jeon Hong-jae, a professor of oncology at Bundang CHA Hospital, said on the 13th, “Immunotherapy anti-cancer drugs that can expect long-term survival in patients who respond well to the medication and are less effective in patients who do not respond to the medication are like ‘all or nothing’,” and “the first phase of clinical trials.” “The drug’s value is sufficient even with the proof of OS improvement used as an indicator,” he said.
The American Association of the Liver Association’s liver cancer clinical trial guidelines also state, “PFS may be an appropriate treatment effect evaluation index for other solid cancer research, but since liver cancer may be subject to confounding factors such as death due to deterioration of liver function, it is better to evaluate it with OS, which is a direct clinical index. “It is more appropriate.”
The reason OS improvement in liver cancer is significant is because of the characteristics of the cancer. The goal of treatment for liver cancer, which is diagnosed when the disease is already in an advanced stage, is to improve survival rate. This is why many treatments are developed with the goal of extending overall survival (OS).
Liver cancer is an organ that has a significant impact on overall health. Professor Jeon recently published research results showing that the risk of death in patients with reduced liver function after liver cancer treatment is higher than the risk of death in patients whose liver cancer worsens during treatment. This means that in order to improve the survival rate of liver cancer patients, it is important to manage their overall health well.
Many liver cancer immunotherapy clinical trials also evaluate OS improvement as the primary indicator. The primary evaluation indicator for Imfinzi + Imudo as well as BMS’s Opdivo + Yervoy combination therapy is OS improvement.
Professor Jeon said, “In order to see the median PFS, we need to see where 50% of the patients fall into, but it is not easy to satisfy even that in clinical trials of liver cancer immunotherapy drugs,” adding, “We have already improved OS as a primary indicator and received approval from the U.S. Food and Drug Administration (FDA). “There is no need to worry too much about PFS because I received it,” he said.
Korea’s liver cancer mortality rate is the highest in the Organization for Economic Co-operation and Development (OECD). The 5-year survival rate for liver cancer patients is 39.3%, which is half of the 5-year survival rate for all cancers (72.1%). The 5-year survival rate for patients with distant metastatic liver cancer is only 3.1%.
Although many treatments are being developed to overcome liver cancer, the survival rate improvement is not as fast as that of other cancers. Over the past 10 years, the 5-year relative survival rate has only increased by 1%.
The liver is an organ that detoxifies toxic substances entering the body. To eliminate cancer, highly toxic drugs must be administered, but if anticancer drugs are also administered to a liver whose function has declined due to cancer, the patient will not be able to withstand it. This is why chemical toxic anti-cancer treatment is not used well for liver cancer.
Targeted anticancer drugs such as Nexavar and Lenvima are being used to treat liver cancer, but there are limitations in improving patient survival rates. Immunotherapy drugs, such as Roche’s Tecentriq, are undergoing changes as they are being used one after another to treat liver cancer. This is because immunotherapy drugs that increase the body’s immune system’s ability to attack cancer can eliminate cancer while minimizing liver function decline.
The immunotherapy combination therapy, which combines the CTLA-4 inhibitor ‘Imudo’, which activates immune T cells, and the PD-L1 inhibitor ‘Imfinzi’, is the first liver cancer treatment to demonstrate long-term survival of 4 years.
The 4-year OS of patients who received this treatment was 25.2%. This means that one out of four patients continues to live for more than four years. The 5-year survival rate, which is considered the standard for cancer cure, is 19.6%. The advantage over Nexavar (9.4%), an existing targeted anticancer drug, was clearly confirmed.
Global pharmaceutical companies’ challenge to conquer liver cancer continues. BMS Opdivo and Yervoy combination therapy, which combines two immunotherapy drugs, is also considered a promising treatment for liver cancer. We are speeding up follow-up research by using it for primary liver cancer treatment and demonstrating a 2-year OS of 49%.
Roche is conducting follow-up clinical trials to confirm the effectiveness of liver cancer treatment by adding tiragolumab, a new TIGIT-type immunotherapy agent, to the combination of the immunotherapy drug Tecentriq and the targeted anticancer drug Avastin.
Reporter Lee Ji-hyeon bluesky@hankyung.com
