Drug combination makes curative surgery possible for liver cancer

Aug. 2, 2021

A combination of the kinase-inhibitor drug cabozantinib and the immunotherapy drug nivolumab can make curative surgery possible in some liver cancer patients who would normally not be considered surgery candidates.

Results published July 29 in the journal Nature Cancer by researchers at the Johns Hopkins Kimmel Cancer Center describe the benefits of this drug combination. Among 15 people with hepatocellular carcinoma (HCC) in the study who could not be treated previously with surgery, the drugs allowed 12 patients to undergo successful surgical removal of their cancer. Five of these 12 patients had only 10% or less of their tumor remaining after the drug treatment.

The combination therapy offers a much-needed treatment for HCC, which makes up more than 90% of all primary liver cancers and is the fourth leading cause of cancer-related death worldwide. Fewer than 30% of HCC cases globally can be surgically resected at the time of diagnosis, either because the liver is too damaged or the cancer has spread into tissues that make surgery too difficult.

HCC is unusual among solid-tumor cancers because there have been no systemic therapies used to treat the cancer to make it more amenable to surgery, says Mark Yarchoan, MD, Assistant Professor of Oncology at the Johns Hopkins University School of Medicine and senior author. “We had a hunch that there were patients who were currently incurable that we could get to a surgery who would do well, and sure enough, there was a group of patients who participated in this study who are alive today without tumor who would not have been offered surgery before.”

The findings also suggest that the drug combination could help with rates of cancer recurrence after surgery. Even among patients who have successful surgeries, the rate of recurrence can be 50% or higher. In the current study, the researchers found that the five patients who underwent surgery and had their tumors shrink significantly have remained disease free for more than 230 days so far. Four of the seven patients who did not have a significant tumor response developed disease progression between 56 and 155 days after the end of treatment.

Cabozantinib and nivolumab have been used separately and in combination to treat advanced liver cancer before, but the researchers wanted to test their use specifically to see whether they could make more patients eligible for potentially curative surgery.

All of the patients were recruited from the Kimmel Cancer Center’s Liver and Biliary Cancer Multidisciplinary Clinic.

The research team took a closer look at the immune response and tumor microenvironment in blood and tissue biopsies from patients enrolled in the study to learn more about exactly how HCC responded — or didn’t respond — to the combination treatment. 

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