Factors in Choosing First-Line Targeted Therapy in RCC

Shilpa Gupta, MD

Several oral VEGF tyrosine kinase inhibitors (TKIs) are approved for first-line treatment of metastatic renal cell carcinoma (RCC).Targeted Oncologyspoke with Shilpa Gupta, MD, genitourinary oncologist, Moffitt Cancer Center, and assistant professor of Oncology and Internal Medicine, University of South Florida Morisani College of Medicine, on considerations in choice of therapy.

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

Dr. 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 patient-reported 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?

Dr. Gupta:[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 sunitinb. 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?

Dr. Gupta: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?

Dr. Gupta: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?

Dr. Gupta: For kidney cancer, we do CT scans about every 8 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?

Dr. Gupta: