Presurgery treatment with a combination of Cabometyx (cabozantinib) and Opdivo (nivolumab) for hepatocellular carcinoma may shrink tumors enough to make liver cancer patients eligible for surgical resection, according to findings published in Nature Cancer.
Over time, hepatitis B, hepatitis C, fatty liver disease and other causes of liver injury can lead to the development of liver cancer. Around 90% of all liver cancer cases are a type known as hepatocellular carcinoma (HCC). HCC often has no symptoms at early stages, and many people are diagnosed late. Surgically removing a part of the liver can help treat and in some cases even cure liver cancer. But around the world, less than 30% of individuals with HCC qualify for the surgery, usually because their tumors are already too large or the cancer has spread.
“The patients who are enrolled in this study are typically just thought of as incurable in the current conventional sense, so the fact that we saw these responses was really exciting, because this suggests this strategy could be adopted for very challenging incurable diseases,” the study’s first author, Won Jin Ho, MD, of the Johns Hopkins University School of Medicine in Baltimore, said in a press release.
Neoadjuvant therapy is typically administered prior to surgery or other primary treatment with the aim of downgrading tumor size or tackling smaller numbers of metastasized cancer cells. Ho and colleagues carried out a small study (ClinicalTrials NCT03299946) to assess the use of Cabometyx in combination with Opdivo as a neoadjuvant systemic therapy for people with HCC, including those who would not presently qualify for surgery. Cabometyx is a targeted therapy that interferes with cancer cell growth. Opdivo is an immunotherapy that helps the immune system fight cancer.
“We wanted to use a combination that reflected the standard of care,” senior study author Robert Yarchoan, MD, also of Johns Hopkins, said in the press release. “This combination reflected where we feel the field is going in terms of using two drugs together to try to maximize the therapeutic effects.”
Of the 15 individuals treated with the two-drug combination, 12 (80%) had successful surgery, leaving behind no cancer cells at the margin of the resection. Five participants (42%) had only a minimal amount of cancer posttreatment, showing a strong pathological response.
The drug combination also appeared to lower the risk of post-surgery recurrence. Following resection, five individuals who showed significant tumor shrinkage did not experience recurrence for more than 230 days.
Analyzing tumor specimens and blood samples, the researchers found that those who responded well to the combination therapy had more cancer-fighting T cells in their tumors as well as a distinct pattern of B cells, suggesting that B cells contribute to antitumor immunity in people with HCC.
“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,” wrote the researchers.
Click here to read the study abstract in Nature Cancer.