Liver cancer, specifically its most common form, hepatocellular carcinoma (HCC), was historically difficult to treat in advanced stages. The arrival of immunotherapy, which uses the body’s immune system to fight cancer, has marked a new chapter in managing this disease.
Understanding Immunotherapy for Liver Cancer
Immunotherapy for liver cancer works by revealing cancer cells to the immune system. T-cells, a type of immune cell, patrol the body for threats, but some cancer cells use “checkpoint” proteins like PD-L1 to evade detection. These proteins bind to corresponding proteins (like PD-1) on T-cells, acting as a brake on the immune response and allowing the cancer to grow. Immunotherapy drugs called checkpoint inhibitors block this interaction. By interfering with PD-1 or PD-L1, these medications release the brakes on T-cells, enabling them to recognize and attack liver cancer cells.
This mechanism differs from chemotherapy, which uses drugs to kill rapidly dividing cells, affecting both cancerous and healthy tissue. Immunotherapy is more targeted, as it aims to restore the immune system’s natural ability to identify and eliminate malignant cells.
Defining and Measuring Success
To understand immunotherapy’s effectiveness, it is necessary to know how success is defined in medical studies. Researchers use several metrics, called endpoints, to measure how well a treatment works in a clinical trial.
One of the primary metrics is Overall Survival (OS), which measures the length of time patients live after starting a new treatment. A longer median OS for a new therapy compared to an older one suggests it is more effective at extending life. This endpoint directly measures a treatment’s ability to help patients live longer.
Another measurement is Progression-Free Survival (PFS), which is the length of time a patient lives with the cancer without it growing or spreading. A longer PFS indicates that the treatment is successfully controlling the cancer for a period and halting the disease’s advancement.
A third endpoint is the Objective Response Rate (ORR), the percentage of patients whose tumors shrink by a predefined amount in response to treatment. The ORR provides insight into how many patients’ tumors visibly respond to the therapy. Together, OS, PFS, and ORR offer a comprehensive picture of a treatment’s effectiveness.
Reported Success Rates from Clinical Trials
The understanding of immunotherapy’s effectiveness in liver cancer is shaped by clinical trials. One study, IMbrave150, evaluated a combination of atezolizumab (a PD-L1 checkpoint inhibitor) and bevacizumab (a drug that stops tumors from forming new blood vessels). This combination was compared to sorafenib, the previous standard of care.
Patients who received the atezolizumab and bevacizumab combination had a median overall survival of 19.2 months, compared to 13.4 months for those on sorafenib. The combination also improved progression-free survival to a median of 6.8 months versus 4.3 months for sorafenib. The objective response rate was 27% for the combination group, compared to 12% for the sorafenib group.
Another study, the HIMALAYA trial, tested a different immunotherapy approach. This trial used a combination of durvalumab (a PD-L1 inhibitor) and a single dose of tremelimumab, which targets the CTLA-4 immune checkpoint. This regimen, known as STRIDE, was also compared to sorafenib.
The HIMALAYA trial demonstrated a long-term survival benefit. After three years, 30.7% of patients who received the STRIDE regimen were still alive, compared to 20.2% of those treated with sorafenib. This study highlighted the potential for immunotherapy combinations to produce durable responses in a subset of patients.
Factors That Influence Treatment Response
The success of immunotherapy is not uniform, as several factors influence how a person’s cancer responds to treatment.
- Cancer stage: The data from major trials applies to patients with advanced or unresectable HCC, meaning cancer that cannot be removed with surgery. Immunotherapy is most established as a treatment for these later stages.
- Liver function: Since HCC develops in the liver, the organ’s health is important. Doctors use scoring systems, like the Child-Pugh score, to assess liver damage, and patients with better-preserved function have better outcomes.
- Cause of liver disease: Liver cancer is often caused by chronic hepatitis B or C, alcohol-related liver disease, or nonalcoholic steatohepatitis (NASH). The response to immunotherapy may differ depending on the initial cause.
- Overall health: A patient’s general health, measured by a performance status score like ECOG, also influences outcomes, as those who are more active tend to respond better to treatment.
The Role of Immunotherapy in Treatment Plans
Based on clinical trial results, immunotherapy combinations are now a central part of the treatment strategy for advanced liver cancer. Regimens like atezolizumab plus bevacizumab are now a first-line treatment for eligible patients with unresectable HCC. This is the first treatment recommended after diagnosis of advanced disease.
For about a decade, oral medications like sorafenib were the primary first-line option. The superior outcomes seen with modern immunotherapy combinations led to their adoption as the new benchmark.
The STRIDE regimen (durvalumab plus tremelimumab) is another approved first-line option. Older drugs like sorafenib or lenvatinib are now reserved as second-line treatments. They are used if a patient’s cancer progresses after initial immunotherapy or if the patient is not a suitable candidate for it.