Original Research

Cardiovascular Effects of Tyrosine Kinase Inhibitors in Patients With Advanced Renal Cell Carcinoma at the VA San Diego Healthcare System

Fed Pract. 2019 May;36(suppl 3):S47-S52

References

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Discussion

Of the available oral TKI therapies for RCC, sunitinib and sorafenib have the most data associated with nonhypertensive CV toxicity.^2,7-10,12 Instudies, the percentage of patients who experienced CV toxicity while on sunitinib or sorafenib has ranged widely, from 2.7% to 33.8%; the variance may be attributable to differences in how institutions report CV toxicities.^7-9

According to the prescribing information for TKIs, hypertension is frequently reported as an AE for all 5 TKIs, and BP monitoring is recommended.^3,4 However, the development of hypertension with these TKIs has been associated with response to therapy.⁷ With pazopanib, sorafenib, and sunitinib, there is a higher incidence of other AEs: edema, HF, MI, and QTc prolongation. Baseline ECG is recommended for all patients started on pazopanib and sunitinib and for patients with a history of CVD who are started on sorafenib. An ECG is recommended for patients with a history of CVD who are started on pazopanib and sunitinib.

Even with the medication prescribing information recommendations, it is unclear how frequently patients should be monitored. At VASDHS, CV monitoring for any patient started on a TKI remains at the discretion of the oncologist. There are concerns that ordering cardiac monitoring tests, which might be unnecessary, will change or guide therapy. In this study, data evaluation revealed 1 patient who experienced a CV event had a CVD history that was not documented in the patient’s medical history. It is important that providers obtain a detailed clinical assessment of patients CV history during each visit to determine whether CV monitoring should be considered. Patients also may benefit from additional counseling to emphasize the importance of adherence to CV medication therapy to reduce the incidence of these events.

Data from this study indicate that routine CV monitoring should be considered in patients with CVD, in keeping with current medication prescribing information recommendations. Of the patients who had a CV event, 54% experienced hypertension, 18% MI, and 28% stroke, QTc prolongation, or congestive HF.

All these patients had a history of CVD, but many did not undergo baseline CV monitoring (Table 3) at the start of therapy. Thus, it was difficult to determine whether these patients’ CV events could have been prevented with baseline monitoring. However, baseline and routine cardiac monitoring within the first 4 months of therapy may help identify worsening CV function.

Limitations

This retrospective study had several limitations. Many patients did not have a baseline cardiac monitoring test or any monitoring during therapy. Often, a cardiac test was performed only when the patient was symptomatic or experiencing a CV event. In addition, because of intolerance or nonadherence to therapy, many patients discontinued treatment early, before completing 30 days. That axitinib and cabozantinib are newer therapies and not first-line at VASDHS during the data collection period accounts for the small number of patients on these therapies. Therapy was shorter for patients started on pazopanib, axitinib, and cabozantinib than it was for patients on sunitinib and sorafenib. Duration of therapy may affect treatment-related events, but the majority of patients in this study experienced an event within 4 months of therapy. About half of the patients who experienced an event were nonadherent to their CV medication regimen. Another potential limitation is that this study was conducted at VASDHS, where most patients are male (RCC incidence is 2:1 male:female).