Liver cancer is one of the leading causes of cancer-related deaths worldwide. In 2007, the drug sorafenib was approved as a treatment for people with a type of liver cancer that can’t be removed, known as non-resectable liver cancer. Patients using this drug by itself survived on average for around 10-12 months. To increase this survival rate, scientists wanted to investigate whether combining several medications could provide better results for these patients. 

In 2020, doctors changed the first line of treatment for non-resectable liver cancer to a combination of two medications, atezolizumab and bevacizumab, instead of sorafenib alone. These medications are immunotherapy drugs, meaning they help the body fight cancer by either suppressing or activating the immune system. 

Atezolizumab works by inhibiting proteins found in cancer cells, which slows growth of the cancer. It does this by obstructing the signals cancer cells use to suppress immune cells, so the immune cells can better fight the cancer. Bevacizumab helps your body fight cancer from a different angle, by preventing the cancer cells from forming new blood vessels. Without new blood vessels, cancer cells in the tumor will be deprived of nutrients and grow more slowly, allowing the body more time to fight against them. 

An international group of researchers recently followed up on a previous study that tried a combination of atezolizumab and bevacizumab to treat non-resectable liver cancer. Since scientists had previously shown success with this combination of drugs in the short term, these researchers wanted to assess whether they could help extend patients’ lives in the long term. 

The researchers selected 501 patients with liver cancer and randomly placed them in two groups. One group was administered sorafenib orally twice a day, while the other group received a combination of atezolizumab and bevacizumab every three weeks via IV. The researchers followed up with each patient to review their progress. 

The researchers found the patients who received the combination of drugs had an average overall survival rate of a little over 19 months, with about 7% of patients progression free, meaning their cancer did not get worse. Patients treated with sorafenib had an overall survival rate of a little over 13 months, with about 4% of patients progression free. 

Patients who received the combination of drugs also had less side effects than those who received sorafenib alone. The authors found 86% of patients reported side effects with the combination of drugs, while 95% of patients reported side effects with sorafenib. Although there were fewer side effects associated with the combination of drugs, those side effects caused 22% of the participants to withdraw from the study. The side effects included protein in urine, high blood pressure, indicators of liver disease, and fatigue. 

One issue reported by the sorafenib group was a common side effect of immunotherapy drugs called palmar-plantar erythrodysesthesia syndrome. This syndrome causes diarrhea, along with redness, swelling, and blistering of the hands and feet. The researchers noted the same side effects were observed in the previous study, suggesting the duration of the combination of drugs did not increase the amount or intensity of side effects. 

The team concluded a combination of atezolizumab and bevacizumab could prolong survival in patients with unresectable liver cancer, justifying this combo as the new standard treatment. However, they acknowledged some limitations of the study, including the small number of participants and the fact they were not evaluated for other contributing factors, like genetics or alcohol consumption. They suggested future work should focus on how biological and environmental factors like these might change the treatment’s success.

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