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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.
Comment: In addition to this negative study, negative results from part A of the CheckMate 914 study were recently presented at the 2022 ESMO Congress (Ann Oncol 2022; 33:suppl 7:S808). The study compared the combination of adjuvant nivolumab plus ipilimumab with placebo in patients with renal cancer at high risk after nephrectomy and failed to demonstrate an improvement in the primary endpoint of DFS. A recent update of KEYNOTE 564 continued to demonstrate a DFS benefit, but assessment of overall survival remains immature.
Given the variable findings from these studies, it is hard to see a “standard of care.” That said, the data from KEYNOTE 564, in my view, warrant discussion with high-risk patients and a shared decision regarding administration of adjuvant pembrolizumab.
Pal SK et al.
Title: Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): A multicentre, randomised, double-blind, phase 3 trial.
Source: Lancet 2022 Sep 10; [e-pub]. (Abstract/FREE Full Text)