Dr. George on Dosing TKIs in RCC

Daniel J. George, MD
Published: Tuesday, Mar 19, 2019



Daniel J. George, MD, professor of Medicine and Surgery, member, Duke Cancer Institute, discusses the importance of dosing TKIs properly in patients with renal cell carcinoma (RCC).

Although the S-TRAC trial showed the benefit of adjuvant therapy with sunitinib (Sutent) in patients with high-risk stage III disease, there has not been as much of an uptake due to prior negative studies. For example, the ASSURE study looked at sunitinib, sorafenib (Nexavar), and placebo in the adjuvant setting, and demonstrated no difference in disease-free survival (DFS). However, many patients were dose-reduced to as low as 25 mg of sunitinib, says George. More than halfway into the study, the dose protocol was reduced from 50 mg to 37.5 mg, which most likely resulted in decreased efficacy, he adds.

In the PROTECT study, investigators had to change the initial adjuvant dose of pazopanib (Votrient) from 800 mg to 600 mg halfway through due to tolerance. In patients who started at 800 mg, investigators noted a statically significant improvement in DFS similar to what was observed in S-TRAC. However, in the patients who had the dose reduction from the beginning, the benefit was not determined to be statistically significant.

Therefore, dose matters when it comes to the adjuvant setting, says George. The issue is that a higher dose also results in added toxicity. Learning how to balance that is key, he adds. Identifying patients who have an ECOG performance status of 0 following surgery is important in finding that balance, as is counseling patients on tolerability and being proactive with dose interruptions, rather than dose reductions. If this approach is adopted, there are patients who will be able to benefit and tolerate TKIs in the adjuvant setting.
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Daniel J. George, MD, professor of Medicine and Surgery, member, Duke Cancer Institute, discusses the importance of dosing TKIs properly in patients with renal cell carcinoma (RCC).

Although the S-TRAC trial showed the benefit of adjuvant therapy with sunitinib (Sutent) in patients with high-risk stage III disease, there has not been as much of an uptake due to prior negative studies. For example, the ASSURE study looked at sunitinib, sorafenib (Nexavar), and placebo in the adjuvant setting, and demonstrated no difference in disease-free survival (DFS). However, many patients were dose-reduced to as low as 25 mg of sunitinib, says George. More than halfway into the study, the dose protocol was reduced from 50 mg to 37.5 mg, which most likely resulted in decreased efficacy, he adds.

In the PROTECT study, investigators had to change the initial adjuvant dose of pazopanib (Votrient) from 800 mg to 600 mg halfway through due to tolerance. In patients who started at 800 mg, investigators noted a statically significant improvement in DFS similar to what was observed in S-TRAC. However, in the patients who had the dose reduction from the beginning, the benefit was not determined to be statistically significant.

Therefore, dose matters when it comes to the adjuvant setting, says George. The issue is that a higher dose also results in added toxicity. Learning how to balance that is key, he adds. Identifying patients who have an ECOG performance status of 0 following surgery is important in finding that balance, as is counseling patients on tolerability and being proactive with dose interruptions, rather than dose reductions. If this approach is adopted, there are patients who will be able to benefit and tolerate TKIs in the adjuvant setting.

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