No Benefit of Adjuvant Antiangiogenic Drugs in Renal Cell Carcinoma

Adjuvant treatment with the oral antiangiogenic drugs sorafenib and sunitinib doesn’t improve survival after complete resection of non-metastatic renal cell carcinoma (RCC), reports a placebo-controlled trial in The Lancet.

The study included 1943 patients with completely resected, non-metastatic clear- cell or non-clear cell RCC considered at high risk of recurrence. After stratification for recurrence risk and other characteristics, patients were randomly assigned to 54 weeks of treatment with sunitinib, sorafenib, or placebo. Disease-free survival was assessed by intention to treat.

The two active treatments had high rates of discontinuation related to toxic effects: 44 percent with sunitinib and 45 percent with sorafenib. This prompted reduction in the starting doses, which were then titrated up to the original full doses. However, toxicity remained high even at the reduced dosing regimen.

The trial was halted early owing to low conditional power for the primary endpoint. Disease-free survival was not significantly different between groups: median 5.8 years with sunitinib, 6.1 years with sorafenib, and 6.6 years with placebo. Frequent grade 3 adverse events included hypertension, hand-foot syndrome, rash, and fatigue. There were five deaths either related to treatment or occurring within 30 days after the end of treatment.

Renal cell carcinoma is a highly vascular tumor, proliferating via dysregulation of the vascular endothelial growth factor pathway. Sunitinib and sorafenib have been shown to improve survival in patients with advanced renal cell carcinoma [Haas NB, et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN e2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016; Mar 8. pii: S0140-6736(16)00559-6. doi: 10.1016/S0140-6736(16)00559-6].