Combining Immunotherapy With VEGFR-Targeted Therapy
For patients with unresectable or metastatic hepatocellular carcinoma, treatment increasingly relies on combinations that attack both the tumor and the tumor microenvironment.
One important regimen combines camrelizumab, a PD-1 immune checkpoint inhibitor, with rivoceranib, also known as apatinib, an oral tyrosine kinase inhibitor targeting VEGFR2.
The rationale for this combination is complementary.
Camrelizumab helps T cells recognize and attack tumor cells by blocking PD-1 signaling.
Rivoceranib reduces VEGF-driven blood-vessel formation by inhibiting VEGFR2. In addition to restricting tumor blood supply, suppression of abnormal tumor vasculature may create a more favorable environment for immune cells.
The combination can therefore be viewed as:
PD-1 immunotherapy + anti-angiogenic targeted therapy
without conventional cytotoxic chemotherapy.
In the international phase III CARES-310 trial, the combination was compared with sorafenib as first-line treatment for unresectable hepatocellular carcinoma.
Initial results showed median progression-free survival of 5.6 months versus 3.7 months and median overall survival of 22.1 months versus 15.2 months.
With longer follow-up, median overall survival reached approximately 23.8 months with camrelizumab plus rivoceranib compared with 15.2 months with sorafenib.
Patients who may be considered for this approach generally have:
- Hepatocellular carcinoma that cannot be surgically removed or treated curatively with local therapy
- Metastatic hepatocellular carcinoma
- Adequate liver reserve
- Acceptable blood pressure and cardiovascular status
- No contraindication to immune checkpoint inhibition
Because many patients with liver cancer also have cirrhosis or chronic hepatitis, careful assessment of liver function is essential before treatment.
Important adverse effects can include hypertension, hand-foot skin reactions, liver-enzyme abnormalities, proteinuria and immune-related reactions.
For selected patients, this treatment combines immune activation and tumor blood-vessel inhibition and provides a chemotherapy-free first-line systemic option for advanced hepatocellular carcinoma.
