Effective Adjuvant Therapy for High-Risk Renal Cancer: The Search Continues

Metastatic renal cell cancer remains an incurable, albeit treatable, disease, thus the search continues for effective adjuvant therapy for patients at high risk for systemic failure following curative-intent nephrectomy. Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, was approved by the FDA for use in metastatic renal cancer based on improved progression-free survival compared to placebo in the salvage setting. Now, in a partly industry-funded, randomized, multicenter, phase 3 study, investigators evaluated 1 year of adjuvant everolimus (10 mg daily) versus placebo in patients with renal cancer at high or very high risk for systemic recurrence after nephrectomy.

The risk of recurrence was based on a modification of the UCLA Integrated Staging System. Patients were required to have good performance status and normal organ function. Of 1545 patients enrolled over a 5-year period, median age was 58 years, 91% were white, and 83% had clear cell histology.

At a median follow-up of 76 months, recurrence-free survival (RFS), the primary end point, was longer with everolimus than with placebo (hazard ratio, 0.85; P=0.051; 5-year RFS, 67% vs. 63%; P=0.050), but the pre-specified P value for statistical significance of 0.044 was not met. In the everolimus arm, 47% of patients did not start treatment or discontinued treatment early; median time on study treatment was 9.3 months versus 12.6 months in the placebo group. Grade 3 and higher adverse events occurred in 46% of patients in the everolimus arm versus 11% in the placebo arm.