Findings from the phase III JAVELIN Renal 101 Trial show that patients with advanced renal cell carcinoma and high baseline serum troponin T levels are at a greater risk of major adverse cardiac events during treatment with a combination of immune checkpoint inhibitor (ICI) avelumab and vascular endothelial growth factor receptor (VEGFR) inhibitor axitinib.

Researchers compared the incidence of major adverse CV events (MACE) and also changes in LVEF or baseline levels of serum cardiac biomarkers in 886 patients with advanced renal cell carcinoma receiving avelumab + axitinib versus sunitinib. Patients were randomly assigned to receive IV avelumab (10 mg/kg) every 2 weeks + axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). 

Results reported in the Journal of Clinical Oncology show that overall 31 patients (7.1%) receiving combination treatment experienced a major cardiac event compared to 17 patients (3.9%) in sunitinib alone treatment group, a difference which was nonsignificant.

Among patients receiving the avelumab + axitinib combination treatment, those who had higher baseline troponin T values were at greater risk of MACE vs patients with lower troponin T levels; 17.1% vs 5.2%, respectively. No such significant association was noted in patients treated with sunitinib; 5.1% vs 5.7%, respectively. Decrease in LVEF was more common in the combination treatment group (8.5% vs 1.6%, respectively), but most patients recovered and no other significant cardiac events or symptoms were reported. “No significant association was noted between other serum cardiac biomarkers and cardiovascular baseline risk factors and MACE”.

The researchers therefore concluded that advanced renal cell carcinoma patients with high baseline troponin T levels should be carefully monitored for occurrence of adverse cardiac events while receiving the combination of avelumab and axitinib, especially in patients who have cardiovascular risk factors. Monitoring of LVEF as a routine is not recommended in asymptomatic patients since the decline in LVEF recovered in most patients on combination treatment. However, the authors write that “cardiac history should not exclude patients from receiving ICI plus VEGFR combination therapy” but “a cardiologist should be involved in patient management from the outset of treatment”.

Reference

1. Rini BI, et al. Prospective cardiovascular surveillance of immune checkpoint inhibitor-based combination therapy in patients with advanced renal cell cancer: data from the phase III JAVELIN Renal 101 Trial. J Clin Oncol. 2022 Mar 3;JCO2101806. doi: 10.1200/JCO.21.01806.