Researchers have identified a potential biomarker that may indicate patient response to sorafenib, a common chemotherapy treatment for liver cancer, according to a new study published in JCI Insight.
 
Although regorafenib, ramucirumab, cabozantinib, and lenvatinib are newly-approved targeted therapies for the treatment of advanced hepatocellular carcinoma (HCC), sorafenib remains the standard of care. However, the researchers noted that treatment-associated toxicities are frequent, often causing missed doses and therapy discontinuation. In addition, relatively low response rates to current immunotherapeutic approaches pose a challenge in treating this population. Accurately identifying which patients will benefit from the therapy could help to better individualize therapeutic options.
 
For the study, the researchers analyzed blood samples from 30 patients both before and at 2 timepoints during treatment with sorafenib. They observed elevated levels of CD8+ cytotoxic T-cells producing interferon type 2, which were associated with improved progression-free survival (PFS) and overall survival (OS). High levels of these T cells were correlated with a significantly reduced risk of death over time, according to the study.
 
In addition, the study showed that patients with a high ratio of CD4+ T-effector/T-regulatory cells prior to treatment demonstrated a significant improvement in PFS and OS, as well. The researchers noted that decreased numbers of PD-1 and CTLA-1 on T-cells may indicate that a combination of sorafenib with checkpoint inhibitors, such as nivolumab and pembrolizumab, could be a promising treatment option.
 
“Studying biomarkers that correlate with progression-free or overall survival can help reduce exposure to therapies that have an impact on a patient’s quality of life and survival,” lead author Yasmin Thanavala, PhD, said in a press release. “Utilizing this information, our evidence supports the rationale that patients could benefit from a regimen of sorafenib and immunotherapy, which could help with antitumor immunity and improve the magnitude and strength of antitumor responses.”
 
With appropriate biomarkers, predicting therapeutic benefit could help reduce exposure to toxic therapies that would have a significant effect on cost, quality of life, and patient survival, the researchers concluded.

 
References
 
Thanavala Y, Iyer R, Kalathil SG, et al. Augmentation of IFN-γ+ CD8+ T cell responses correlates with survival of HCC patients on sorafenib therapy. JCI Insight. Doi: 10.1172/jci.insight.130116
 
Roswell Park Researchers Identify Immune Biomarker of Response in Patients with Advanced Liver Cancer [news release]. Roswell Park Comprehensive Cancer Center. https://www.roswellpark.org/media/news/roswell-park-researchers-identify-immune-biomarker-response-patients-advanced-liver. Accessed August 12, 2019.