High serum troponin T levels at baseline are associated with a higher risk of major adverse cardiovascular events (MACE) in patients with advanced renal cell carcinoma (RCC) who receive treatment with avelumab and axitinib, new research suggests.
Patients who had high baseline troponin T levels had a more than 3-fold greater risk of MACE, but this association was only seen in patients treated with avelumab and axitinib, not in those treated with sunitinib.
These results, from the phase 3 JAVELIN Renal 101 trial, were published in the Journal of Clinical Oncology.
According to researchers, JAVELIN Renal 101 (ClinicalTrials.gov Identifier: NCT02684006) is the first randomized trial of an immune checkpoint inhibitor (ICI) and a VEGFR inhibitor that included evaluations of serum cardiac biomarkers and left ventricular ejection fraction (LVEF).
The trial’s safety population included 873 patients with advanced RCC — 434 who received avelumab plus axitinib and 439 who received sunitinib. The proportion of patients with a history of hypertension was 60.9% in the combination arm and 54.5% in the sunitinib arm.
At the first interim analysis, the median exposure to treatment was 37.2 weeks for avelumab, 39.2 weeks for axitinib, and 31.7 weeks for sunitinib.
MACE (defined as grade 3 or higher cardiovascular adverse events) occurred in 7.1% of patients in the avelumab-axitinib arm and 3.9% of patients in the sunitinib arm. The between-arm difference was not statistically significant, according to the researchers.
In the avelumab-axitinib arm, the incidence of MACE was significantly higher for patients with high baseline troponin T levels than for those with low baseline troponin T levels — 17.1% and 5.2%, respectively (relative risk [RR], 3.31; 95% CI, 1.19-9.22; P =.022).
In the sunitinib arm, there was no significant difference in the incidence of MACE according to baseline troponin T levels (RR, 0.89; 95% CI, 0.2-3.98).
Patients in the avelumab-axitinib arm were more likely to experience a decline in LVEF compared with those in the sunitinib arm — 8.5% and 1.6%, respectively (P <.0001).
However, there was no association between LVEF decline and MACE in either treatment arm. Similarly, there was no association between MACE and hypertension or most other baseline cardiovascular risk factors.
“Patients with high baseline troponin T levels receiving ICI and VEGFR combinations may need to be monitored more closely for MACE,” the researchers concluded. “Routine monitoring of LVEF in asymptomatic patients is not recommended.”
Disclosures: This research was supported by Pfizer as part of an alliance between Pfizer and Merck. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Rini BI, Moslehi JJ, Bonaca M, 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. Published online March 3, 2022. doi:10.1200/JCO.21.01806