Adjuvant Therapy for High-Risk Kidney Cancer: Paradigm Shift?

Patients with locally advanced renal cell carcinoma undergoing curative-intent nephrectomy remain at risk for systemic failure. Studies testing first-generation immunotherapy agents and a variety of tyrosine kinase inhibitors (TKIs) failed to demonstrate benefit, and routine practice is to manage patients expectantly with surveillance imaging. Next-generation immunotherapy agents either in combination or with the addition of TKIs are now the standard of care for metastatic clear-cell disease.

This manufacturer-designed and -conducted phase 3 adjuvant study randomized patients with histologically confirmed renal-cell carcinoma with a clear-cell component at high risk for recurrence to receive 1 year of adjuvant pembrolizumab or placebo. The primary endpoint was investigator-assessed disease-free survival.

Some 994 patients were enrolled. In the treatment and placebo groups respectively, local recurrence was observed in 3.4% and 6.4%, and distant recurrence in 17.3% and 23.5%. Sixty-one percent of patients in the pembrolizumab arm completed all protocol therapy, compared with 74% of those receiving placebo. During a median follow-up of 24 months, 96.6% of treatment versus 93.5% of placebo recipients remained alive. Pembrolizumab recipients had a significantly longer disease-free survival — 77.3% vs. 68.1% (hazard ratio, 0.68).

The observed toxicity of pembrolizumab was consistent with its known side effects: grade 3 or greater adverse events occurred in 32.4% with pembrolizumab versus 17.7% with placebo.