Combining the chemotherapy agent Sutent (sunitinib) with immune checkpoint inhibitors that boost the immune system may help patients with hepatocellular carcinoma (HCC), the most common form of liver cancer.
Preclinical data in HCC mice models shows that the combination of Sutent — the only drug approved by the U.S. Food and Drug Administration (FDA) to treat HCC patients — with an anti-PD-1 antibody significantly reduces tumor growth, compared to either agent alone.
The findings were reported in a University of Missouri study, “Successful chemoimmunotherapy against hepatocellular cancer in a novel murine model,” and published in the Journal of Hepatology.
HCC remains one of the deadliest cancers, with limited clinical options. Although surgery offers a small chance of a cure, most patients are diagnosed at an advanced stage and are not eligible.
In 2008, Sutent became the first FDA-approved drug to treat HCC patients who were ineligible for surgical resection. This multi-targeted receptor tyrosine kinase inhibitor works by killing cancer cells directly, and by suppressing regulatory T-cells, or Tregs. But studies have shown that it only increases median overall survival by about three months — from 7.9 months to 10.7 months.
“While any extension of life is valuable, our research team is developing a new therapeutic strategy that might extend and improve the quality of life for these patients,” Kevin Staveley-O’Carroll, MD, PhD, the study’s lead author, said in a press release.
Immune checkpoint inhibitors have become standard of care in patients with melanoma and lung cancer, and keep showing promise in several other cancer types. These immunotherapies are known to remove the brakes from the tumor-associated immune cells, allowing them to more efficiently recognize and kill tumor cells.
Studies have shown that while HCC tumors are filled with tumor-killing immune cells, 96 percent of them are inactive. This suggests that immunotherapy could be a promising approach to help eradicate such tumors.
To test this hypothesis, researchers at the University of Missouri School of Medicine treated HCC mouse models with either Sutent, an anti-PD-1 antibody, or a combination of both drugs.
Results revealed that the Sunitinit tumoricidal effect and Treg suppression synergized with PD-1 blockade to powerfully suppress tumor growth and activate anti-tumor immunity. Indeed, over a period of four weeks, while the tumors in Sutent-treated mice grew 25 times larger, and those treated with the anti-PD-1 grew 15 times larger, tumors treated with the combination only grew 11 times larger.
“Our results show that a combined chemo-immunotherapeutic approach can slow tumor growth in mice more effectively than either individual treatment,” said Guangfu Li, PhD, DVM, assistant professor in the MU Department of Surgery. “This innovative combination promotes an anti-tumor immune response and better suppresses growth of the cancer. Our findings support the need for a clinical trial to test whether this could become a cost-effective treatment that could help improve the lives of patients with liver cancer.”
