medwireNews: High baseline levels of troponin T may increase the risk for major adverse cardiovascular events (MACE) among advanced renal cell carcinoma (RCC) patients receiving combination treatment with avelumab plus axitinib, suggest data from the JAVELIN Renal 101 trial.
“We suggest that baseline assessment of troponin T levels may be considered when starting treatment with an ICI [immune checkpoint inhibitor] plus a VEGFR inhibitor, particularly in patients with [cardiovascular] risk factors,” say Brian Rini (Vanderbilt University Medical Center, Nashville, Tennessee, USA) and co-researchers.
“Patients with high troponin T levels should be monitored closely for cardiac symptoms during treatment, potentially including [echocardiogram] monitoring, and a cardiologist should be involved in patient management from the outset of treatment,” they continue.
The team notes, however, that “the study provided data only for avelumab plus axitinib,” and “similar prospective studies of other ICI-based combinations are needed to confirm findings and enable broader recommendations to be established.”
The phase 3 trial previously showed significantly improved advanced RCC outcomes among 442 participants who were randomly assigned to receive first-line treatment with the ICI avelumab plus the VEGFR inhibitor axitinib compared with their 444 counterparts who instead received sunitinib.
The researchers now report the results of prospective cardiovascular surveillance during treatment, finding that MACE occurred in a numerically higher proportion of patients in the combination than sunitinib group, at 7.1% and 3.9%, respectively.
But “the difference was not statistically significant, and the difference between arms was reduced in exposure-adjusted analyses,” they write in the Journal of Clinical Oncology.
Various serum cardiac biomarkers were assessed at baseline in subsets of participants, and high levels (defined as above the upper limit of normal) of troponin T were found in around 20% of patients each in the combination and sunitinib groups.
Combination-treated patients with high levels of troponin T (n=35) were significantly more likely than those with low levels (n=135) to develop MACE, at rates of 17.1% versus 5.2%, and a 3.31-fold increased risk with high baseline levels.
There was no such relationship between troponin T levels and MACE risk in the sunitinib arm, and “[o]ccurrence of MACE did not correlate with baseline levels of other cardiac biomarkers in either arm,” say Rini and colleagues.
They also looked at left ventricular ejection fraction (LVEF) and found a significant difference in the proportion that experienced a decline (defined as a ≥10-point reduction from baseline to a value below the lower limit of normal) between the combination and sunitinib groups, at 8.5% versus 1.6%.
However, “most patients recovered, and decline was not associated with other significant cardiac events or symptoms,” highlight the study authors, and therefore “[r]outine monitoring of LVEF in asymptomatic patients is not recommended.”
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J Clin Oncol 2022; doi:10.1200/JCO.21.01806