Sunitinib, Sorafenib Do Not Extend High-Risk Clear Cell RCC Disease-Free Survival

Adjuvant vascular endothelial growth factor–tyrosine kinase inhibitor therapy did not improve disease-free survival in high-risk clear cell renal cell carcinoma ASSURE participants

medwireNews: Secondary analysis of the ASSURE trial has found no evidence of a disease-free survival (DFS) benefit with adjuvant sunitinib or sorafenib for high-risk patients with clear cell renal cell carcinoma (ccRCC).

“Based on this analysis, a rationale for adjuvant therapy in this high-risk population is not elucidated”, say lead investigator Naomi Haas, from the Abramson Cancer Center in Philadelphia, Pennsylvania, USA, and team.

The primary ASSURE trial results did not show a significant DFS gain for the patients with primary resected RCC who were treated for 1 year with either of the vascular endothelial growth factor tyrosine kinase inhibitors (VEGF–TKIs) compared with placebo, the researchers explain in JAMA Oncology.

But they chose to look further at a high-risk subgroup of ccRCC patients with pT3, pT4 or node-positive disease following results from the S-TRAC study of sunitinib versus placebo that showed improved DFS in a similar high-risk population.

However, 5-year rates of DFS in the ASSURE high-risk group did not significantly differ for the 358 patients given sunitinib, the 355 patients given sorafenib and the 356 patients given placebo, at 47.7%, 49.9% and 50.0%, respectively.

Nor did overall survival differ significantly between the groups, with corresponding 5-year rates of 75.2%, 80.2% and 76.5%.  

The researchers write that despite the original starting doses of sunitinib and sorafenib being reduced to combat toxicity, and further dose reductions to allow patients to better manage side effects, there was no significant difference in DFS according to quartiles of dose for either VEGF–TKI. They add that grade 3 side effects occurred in 66% of sunitinib-treated patients and 72% of sorafenib-treated patients versus 28% of those given placebo, “underscoring a high rate of adverse effects” in the trial.

The authors of an accompanying comment note the “divergent” results of the ASSURE and S-TRAC studies and highlight the “remarkably high” treatment discontinuation rates in both. They also point out that at least 50% of patients in both studies were still at risk of an event at time of data reporting.

“Reported findings can change dramatically sometimes on follow-up either due to more events accumulating or emerging out of a subset deriving benefit from the treatment”, observe the commentators Bhupinder Mann and James Zwiebel, from the National Cancer Institute in Bethesda, Maryland, USA.


Haas NB, Manola J, Dutcher JP, et al. Adjuvant treatment for high-risk clear cell renal cancer. Updated results of a high-risk subset of the ASSURE randomized trial. JAMA Oncol; Advance online publication 9 March 2017. doi:10.1001/jamaoncol.2017.0076

Mann B, Zwiebel J. Planning adjuvant trials when regimens effective for patients with advanced disease don’t work in the adjuvant setting–Paradigms lost. JAMA Oncol; Advance online publication 9 March 2017. doi:10.1001/jamaoncol.2017.0066

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