TKI Treatment Choices in mRCC Often Hinge on Dosing, Toxicities

Shilpa Gupta, MD

Genitourinary Oncologist

Moffitt Cancer Center

Assistant Professor, Oncology and Internal Medicine

Morsani College of Medicine

University of South Florida

Tampa, FL

During the past decade, several oral tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) have been approved for the first-line treatment of metastatic renal cell carcinoma (mRCC). Shilpa Gupta, MD, specializes in the treatment of genitourinary malignancies at the Moffitt Cancer Center in Florida, where she also is engaged in research into novel targeted therapies. In this interview with OncologyLive, she discusses considerations in choosing TKIs for her patients.

OncologyLive: Can you go over the factors you use to decide which VEGF TKI to give a patient as an initial therapy?

Gupta: There are three TKIs that are available. For treatment-naïve patients, sunitinib used to be the standard, but recently pazopanib was approved. In my practice, I have started using pazopanib more than sunitinib because of this data, and also I find that there is more consistency of dosing with pazopanib compared to sunitinib, where dosing adjustments are frequently necessary. The COMPARZ trial showed that the efficacy of pazopanib was similar to sunitinib and also that pazopanib was better tolerated. In fact, the patientreported outcomes for pazopanib were better—there were fewer hospitalizations and clinical visits. Also, the PISCES study showed that quality of life was better with pazopanib compared with sunitinib.

What are some of the side effects associated with these TKIs?

[For sunitinib], the major ones are rash and hand-foot syndrome, which is not associated as frequently with pazopanib. Fatigue is also more debilitating with sunitinib. Cardiac toxicities are an issue with these VEGF inhibitors. The incidence is slightly lower with pazopanib. Sorafenib is not generally associated with significant cardiac toxicity. For patients with a cardiac history, I prefer to offer them sorafenib rather than sunitinib or pazopanib. The risk of myelosuppression is also higher with sunitinib compared with pazopanib. Hypertension is also a significant side effect for all of these VEGF TKIs, and that needs to be monitored closely. But even if a patient is hypertensive, the blood pressure can be managed well on these agents.

Patients with a history of significant hepatic issues such as hepatitis or cirrhosis should avoid pazopanib because there is a small incidence of fatal hepatotoxicity. In these cases, sorafenib is a good option, especially since it is also approved for hepatic carcinoma. As an example, I prescribed sorafenib for a patient with alcohol cirrhosis, and he tolerated it very well. Sunitinib is also an option.

How do the side-effect profiles affect the decision?

Every patient is different, and we have to tailor therapies according to each patient’s needs. The side effects certainly determine which agent a patient will have more success with. For older patients, sunitinib is not the best treatment option because of the toxicity, including significant fatigue. If pazopanib is contraindicated, sorafenib can be a good choice for elderly patients, as it is tolerated by most patients.

What else should be considered when choosing a therapy?

The outcome of any successful therapy not only depends on the tumor and the stage of disease, but also on functional status and comorbidities. We always review the risk factors and health history of the patient, which can identify the best therapy for that patient.

Are there molecular tests that can be used to monitor a patient’s response to treatment?

For kidney cancer, we do CT scans about every eight weeks. That is the best test to assess response. Unfortunately, we don’t have any biomarkers yet as part of standard practice.

When a patient stops responding to one TKI, what are the next treatment options?

We do have many options for patients who were prior-treated with a VEGF TKI. Axitinib is another VEGF TKI that is approved for patients who have had a prior TKI. We can offer the patient axitinib, or an mTOR inhibitor such as everolimus, or a clinical trial.