Adjuvant Immunotherapy for Locally Advanced Kidney Cancer: The Saga Continues

Patients with high-risk locoregional renal cell carcinoma have systemic failure rates greater than 50% after partial or radical nephrectomy. Most studies of adjuvant anti-VEGF tyrosine kinase inhibitors and mTOR inhibitors have failed to demonstrate clinical benefit. The FDA approved the PD-1 antibody pembrolizumab for adjuvant use based on evidence of improved disease-free survival (DFS) from the KEYNOTE 564 study.

Investigators performed an industry-funded multinational phase 3 trial of adjuvant atezolizumab (a PD-L1 antibody) versus placebo in patients with clear-cell renal cancer at increased risk for recurrence after nephrectomy (with or without metastasectomy). Patients were stratified based on disease stage, geographical region, and PD-L1 status. The primary endpoint was investigator-assessed DFS in the intent to treat population.

Over 2 years, 778 patients (median age, 60) received either atezolizumab or placebo every 3 weeks for 16 cycles or 1 year. At a median follow-up of 44.7 months, DFS was 57.2 months with atezolizumab and 49.5 months with placebo (hazard ratio, 0.93; 95% CI, 0.75–1.15; P=0.50). Toxicity with atezolizumab was consistent with previous reports; there were no treatment-related deaths.