Atherosclerotic Cardiovascular Risk With Combination Avelumab and Axitinib

Immune Checkpoint Inhibitor Therapy in Oncology

“… 108 These estimates may underestimate the real-world risk, due to under-reporting of cardiovascular events, 109 relatively short follow-up duration (limited use for >5 and particularly >10 years), and selection bias due to stringent inclusion criteria in cancer trials compared with real-world situations. 110 …”

Reply to S. Tan et al

“…We thank Tan et al 1 for their thoughtful review of our article. We agree that oncologists and cardiologists should work together to identify and monitor novel cardiac symptoms and treatment side effects of immune checkpoint inhibitor (ICI)–based combination regimens.…”

“…Furthermore, it is difficult to compare our data, which were obtained from a randomized, phase III, multicenter trial in a defined population of patients with advanced renal cell carcinoma, with real-world data, including the single-institution study reported by Tan et al, 1 which included patients with various tumor types who had received different ICIs (including anti–programmed cell death 1 protein, anti–programmed cell death 1 ligand 1, and anti–cytotoxic T-cell lymphocyte-4 agents) and in which baseline cardiovascular risk factors were not well controlled. We agree with Tan et al 1 that additional research is needed to better assess noninflammatory cardiovascular events that may arise with ICI therapy, especially common events, such as myocardial infarction. In addition, more data are needed to determine the long-term sequelae of immunotherapies, especially as a growing number of patients are successfully treated with ICIs and become cancer survivors.…”

“…In particular, different TKIs were administered in the two arms of the JAVELIN Renal 101 trial (axitinib and sunitinib) 2,3 ; thus, any differences may be due to the attributes of the TKI rather than the addition of an ICI. Furthermore, it is difficult to compare our data, which were obtained from a randomized, phase III, multicenter trial in a defined population of patients with advanced renal cell carcinoma, with real-world data, including the single-institution study reported by Tan et al, 1 which included patients with various tumor types who had received different ICIs (including anti–programmed cell death 1 protein, anti–programmed cell death 1 ligand 1, and anti–cytotoxic T-cell lymphocyte-4 agents) and in which baseline cardiovascular risk factors were not well controlled. We agree with Tan et al 1 that additional research is needed to better assess noninflammatory cardiovascular events that may arise with ICI therapy, especially common events, such as myocardial infarction.…”