Adjuvant VEGF Inhibitors, Sorafenib or Sunitinib, do not Improve Outcomes in Resected Locally-Advanced Renal Carcinoma

Interim results from the ASSURE study

Findings from the ASSURE study suggest that patients with locally-advanced resected renal carcinoma should not be treated with either adjuvant sorafenib or sunitinib. The average period to disease recurrence was similar between those who received sorafenib or sunitinib after surgery and those treated with placebo. The study was presented at the 2015 Genitourinary Cancers Symposium (26-28 February 2015, Orlando, USA).

VEGF inhibitors, sorafenib and sunitinib are widely used for the treatment of metastatic renal cancer. According to the authors, this is the first and largest trial reporting on the efficacy of VEGF inhibitors as adjuvant therapy for patients with locally-advanced renal cancer who are at high risk of recurrence. The current standard of care for such patients is observation.

After undergoing surgery, 1,943 patients with completely resected renal cell carcinoma (pT1b high grade to pT4 any grade, N any) were stratified on risk (intermediate-high or very high), clear/non-clear histology, ECOG performance status, and resection approach, and randomised equally to receive sorafenib, sunitinib, or placebo for one year.

The primary endpoint was disease-free survival (DFS). The study was designed to detect a 25% reduction in the hazard rate, corresponding to an improvement from 5.8 to 7.7 years median DFS.

After accrual of 1,322 patients, the starting dose was reduced and then individually titrated to mitigate the effect of patient discontinuation from treatment intolerance.

At an interim analysis conducted with 62% information, although no efficacy or futility boundaries were crossed, the Data Safety Monitoring Committee recommended release of results.

Recurrence rates (about 40%) and the DFS (5.6-5.7 years) were similar between all three regimens. Researchers continue to follow patients to document recurrence and survival.

The redesign reduced the discontinuation rate on the experimental arms from about 26% in patients starting at full dose to about 14% in patients starting at reduced dose. Most common grade ≥3 adverse events were hypertension (16%/16%/4%), hand-foot reaction (15%/33%/1%), rash (2%/15%/<1%), and fatigue (17%/7%/3%) on sunitinib, sorafenib and placebo, respectively.

Dr Naomi Haas, an Associate Professor of Medicine at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, USA stated that the large specimen collection required for this trial will be an invaluable resource in the mission to cure renal cancer. It will provide molecular clues to identify individuals that may benefit from these treatments and help researchers learn more about therapy resistance and disease recurrence.

Adjuvant treatment of locally-advanced renal cancer is an area of active research. Several trials using other VEGF inhibitors have finished accruing patients and are awaiting analysis. Ongoing clinical trials exploring another VEGF inhibitor, axitinib, and the mTOR inhibitor everolimus are still accruing patients. Trials using immunotherapy and other targeted therapy approaches are being planned.

This study received funding from the US National Institutes of Health.