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• Posted April 24, 2023

Combo Therapy May Prevent Cancer's Return After Liver Surgery

A two-drug combination therapy can enhance survival odds for people with early-stage liver cancer through targeted attacks on tumor cells, a new clinical trial shows.

The combo -- atezolizumab (Tecentriq) and bevacizumab (Avastin) -- reduced risk of cancer recurrence or death by 28% in patients who'd had surgery to remove their liver tumor, researchers report.

This is the first time that any drugs have been shown to lower the risk of liver cancer returning in patients whose tumors were caught early enough to be removable, said researcher Dr. Pierce Chow, a senior consultant surgeon at the National Cancer Centre Singapore.

"In that context, the results of this trial are historical, because for the first time patients with primary liver cancer, if they were to undergo surgical resection or ablation, there's an opportunity for them to receive therapy that can reduce recurrence,"Chow said.

For this clinical trial, Chow and his colleagues tested the two-drug combination on patients with early-stage hepatocellular carcinoma, the most common form of liver cancer.

The atezolizumab/bevacizumb combo already is being used to treat liver cancer that has either spread or can't be treated with surgery. The U.S. Food and Drug Administration approved the combo for this use in 2020.

Atezolizumab blocks the ability of cancer cells to hide from the immune system using a protein called programmed death-ligand 1 (PD-L1). PD-L1 can make a cancer cell appear healthy and thus avoid attack from immune cells.

Meanwhile, bevacizumab blocks a protein called VEGF that makes blood vessels grow. Some cancer cells produce large amounts of VEGF, to encourage the development of new blood vessels that will bring oxygen and nutrition to a tumor.

Given its effectiveness in treating advanced liver cancer, researchers thought the combination therapy might also be useful in preventing the recurrence of early liver cancers.

The main treatments for early-stage liver cancer are surgery or thermal ablation, a treatment that destroys cancer cells with heat or cold, the researchers explained in background notes.

Unfortunately, the risk of liver cancer recurring in these patients runs between 70% and 80%, Chow said.

In the study, 334 patients were recruited; half were randomly assigned to receive the two-drug combo for one year following surgery. The rest were put on active surveillance to see if their cancer returned, which up to now has been the only other option available.

After an average 17 months of follow-up, the combination therapy had reduced risk of recurrence or death by 28% in patients receiving the drugs.

The findings were presented this week at the American Association of Cancer Research annual meeting, in Orlando, Fla. Such research is considered preliminary until published in a peer-reviewed journal.

"This represents a major therapeutic development in the field of liver cancer,"said Dr. Edith Mitchell, a clinical professor of medical oncology with the Sidney Kimmel Cancer Center at Thomas Jefferson University Hospitals in Philadelphia. Mitchell was not involved in the trial.

"The 12-month recurrence rate in the patients who did not receive this therapy was 34%, so this is a very significant and powerful study,"Mitchell said.

Importantly, the combination therapy also did not produce more serious side effects in early-stage liver cancer patients than it does in those with advanced disease, even though these latest patients were on the drugs for longer, both Chow and Mitchell noted.

Patients in the early-stage trial took the combo for about 11 months, on average, compared with about seven months for patients involved in the earlier trials aimed at advanced liver cancer, results showed.

"They were on the therapy significantly longer in terms of the number of months compared to patients on the earlier trial for advanced cancer, but we don't see an increase in side effects in spite of the longer duration of treatment,"Chow said. "And the side effects that we see, most of them are very easily managed."

Chow expects that the sponsor of the clinical trial, drugmaker Genentech/Roche, will soon ask the FDA to approve this new use of the two-drug combo.

In the meantime, researchers plan to continue tracking the health of the patients for around five years, "so further down the line, expect to see more data,"Chow added.

The five-year relative survival rate of patients with early-stage, localized liver cancer is 36%, according to the American Cancer Society.

More information

The U.S. National Cancer Institute has more about atezolizumab (Tecentriq) and bevacizumab (Avastin).

SOURCES: Pierce Chow, MBBS, MMed, FRCS(E), PhD, senior consultant surgeon, National Cancer Centre Singapore; Edith Mitchell, MD, clinical professor, medical oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospitals, Philadelphia; American Association for Cancer Research Annual Meeting and news release, April 16, 2023