ORLANDO—Adjuvant sorafenib and sunitinib do not improve survival for patients with locally advanced renal cell carcinoma (RCC), and were associated with frequent dose reductions and treatment discontinuations, according to initial data from the ASSURE clinical study presented during the 2015 Genitourinary Cancers Symposium.1

“Findings from this study suggest that patients with locally advanced kidney cancer should not be treated with either adjuvant sorafenib or sunitinib,” reported study author Naomi B. Haas, MD, of the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, PA. “Median time to disease recurrence did not differ between those who received sorafenib or sunitinib after surgery (median 5.8 years each) and those treated with placebo (median 6 years).”

“Dose titration reduced the treatment discontinuation rate; this finding may have relevance in other settings,” she noted. “This was the first and largest trial reporting on the efficacy of VEGF inhibitors as adjuvant therapy for patients with locally advanced kidney cancer who are at high risk of recurrence.”

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Because locally advanced RCC is not always cured by surgery, the study authors investigated the oral agents, which are “widely effective” in the metastatic setting, as potential adjuvant therapies.

A total of 1,943 patients with completely resected RCC (pT1b high grade to pT4 any grade N any) were stratified by risk category (intermediate high or very high), clear/non-clear histology, ECOG PS, and resection approach, and were randomly assigned equally to sunitinib daily for 4- or 6-week cycle, sorafenib daily, or placebo, Dr. Haas reported.

However, after 1,322 patients had been enrolled, “the starting dose was reduced and then individually titrated to mitigate the effect of patient discontinuation from treatment intolerance,” Dr. Haas noted.

Participants received assigned treatments for up to 1 year. Disease-free survival (DFS) was the primary study endpoint.

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When the study had accumulated two-thirds of the planned data, an interim analysis was conducted. Efficacy and futility boundaries had not been crossed but the study’s safety monitoring committee recommended release of results.

“There were no significant differences in DFS or overall survival between either of the experimental arms and placebo,” Dr. Haas said. A subgroup analysis of DFS for clear cell RCC similarly found no significant differences among patients administered placebo and those administered adjuvant sunitinib or sorafenib.

“All three study arms did better than expected” in terms of 5-year overall survival, Dr. Hass noted—but there were no significant differences in OS between the experimental and placebo study arms (5-year OS: sunitinib: 76.9% [95% CI: 72.9-81.2%]; sorafenib: 80.7% [95% CI: 77.0-84.6%]; placebo: 78.7% [95% CI: 74.8-82.8%]).

“There is a suggestion that women performed worse on sorafenib than placebo,” Dr. Hass noted.

Frequent grade 3 or higher adverse events included hypertension (16% sunitinib/16% sorafenib/4% placebo), hand̶̶-foot reaction (15%/33%/1%), rash (2%/15%/<1%), and fatigue (17%/7%/3%), Dr. Haas said.


  1. Manola J, Uzzo RG, Flaherty K, et al. Initial results from ASSURE (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma, an ECOG-ACRIN-led, NCTN phase III trial. 2015 Genitourinary Cancers Symposium. Abstract 403.