Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
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
We previously published about this research in a story titled “Predicting Major Adverse Cardiac Events in RCC Treatment” which can be found here. This study was first published in the scientific journal Journal of Clinical Oncology. You can view the full text of the study here.
What Happened?
There are a number of treatments available for renal cell carcinoma, a rare cancer that originates in the kidneys. Two classes of treatment include vascular endothelial growth factor receptor (VEGFR) inhibitors and immune checkpoint inhibitors (ICIs). Unfortunately, both of these types of therapy are known to cause cardiovascular adverse events. In some cases, these therapies are used in combination, increasing the risk of a major cardiac adverse event. In this study, scientists looked at data from the JAVELIN Renal 101 clinical trial in order to identify a potential predictor of these events in patients.
This trial compared a combination treatment of axitinb (a VEGFR inhibitor) plus avelumab (an immune checkpoint inhibitor) against sunitinib monotherapy. The study included a total of 873 patients, and the combination therapy demonstrated superior objective response rate and progression free survival. This was the first trial to also measure serum cardiac biomarkers and left ventricular ejection fraction (LVEF), giving researchers a chance to understand their effects more clearly. While the combination treatment of axitinib plus avelumab was more effective, a greater percentage of patients (7.1 percent) experienced a major adverse cardiac event (MACE).
Patients getting the combination treatment were more likely to see a decline in LVEF; however, this was not associated with MACE. However, it was found that patients receiving this therapy who had higher baseline levels of troponin T were at greater risk for experiencing MACE. In fact, the risk was three times greater. This relationship was not found in patients receiving sunitinib, however.
Overall, the researchers identified high baseline troponin T levels as a risk factor for major adverse cardiac events following treatment with a combination of axitinib and avelumab.
About Renal Cell Carcinoma
Renal cell carcinoma is a cancer of the kidney that generally appears in the lining of the proximal convoluted tubule, a passage in the kidney that transports primary urine. Though generally considered rare, it is the most common type of kidney cancer to affect adults. There are several risk factors that increase a person’s likelihood of getting renal cell carcinoma, such as smoking, obesity, and high blood pressure. Other possible risk factors include long term use of NSAIDs, hysterectomy, certain genetic disorders, family history, and cystic disease of the kidney. This cancer rarely produces symptoms in its early stages, but when it has reached an advanced stage, symptoms may include flank pain, a noticeable abdominal mass, bloody urine, fatigue, fever, night sweats, weight loss and appetite loss, hypertension, and elevated calcium levels. To learn more about renal cell carcinoma, click here.
Why Does it Matter?
Cancer treatments can be hard on the body, and sometimes the side effects can inflict serious harm and misery on patients. In this instance, the risk of potentially life-threatening cardiac events following treatment with a combination VEGFR inhibitor (axitinib) and immune checkpoint inhibitor (avelumab) is increased if the patient displays high levels of troponin T. Therefore, finding a way to potentially predict which patients are at the greatest risk is of vital importance so that they can be monitored and treated accordingly.
This is the conclusion that the researchers who conducted this study reached after evaluating their data, which clearly indicated high troponin T levels as a risk factor for adverse cardiac events. These kinds of discoveries may only seem like incremental improvements, but ultimately they have the potential to improve outcomes for patients living with renal cell carcinoma and save lives.
NOTE: This article was updated for clarity on 4/20/22 to reflect that high troponin T levels in patients taking the combination of axitinib and avelumab is a risk factor for MACE, not the use of the combination treatment alone.
