Adjuvant pembrolizumab plus belzutifan versus placebo in clear cell renal cell carcinoma: a reconstructed survival data analysis of the KEYNOTE-564 and the LITESPARK-022 trials
In brief
Adjuvant pembrolizumab + belzutifan cuts recurrence risk by roughly 45% in high-risk kidney cancer
An analysis combining reconstructed data from the KEYNOTE-564 and LITESPARK-022 trials found that adding belzutifan to pembrolizumab after nephrectomy reduced disease-free survival events by about half compared with placebo. Early overall-survival signals also favored the combination, but follow-up remains limited, so longer data are needed before routine adoption.
- Journal
- ESMO open (Q1)
- Published
- 11 September 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- A Cigliola, A Larcher, B A Maiorano, D Robesti, G Fallara, C Mercinelli, et al.
- PMID
- 42727419
- DOI
- 10.1016/j.esmoop.2026.108543
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 15 September 2026): Reconstructed analysis of adjuvant pembrolizumab + belzutifan
Abstract
BACKGROUND: Adjuvant pembrolizumab improves disease-free survival (DFS) and overall survival (OS) versus placebo in high-risk clear cell renal cell carcinoma after nephrectomy. Recently, pembrolizumab plus belzutifan showed superior DFS over pembrolizumab alone. We assessed the efficacy of adjuvant pembrolizumab plus belzutifan versus placebo using reconstructed data from two pivotal phase III trials. METHODS: Individual time-to-event data were reconstructed from digitised KEYNOTE-564 and LITESPARK-022 Kaplan-Meier curves using a validated algorithm based on numbers at risk. Datasets were pooled to enable indirect comparisons across strategies. The primary endpoint was DFS and OS was secondary. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. FINDINGS: The pooled dataset included 2835 patients. Baseline characteristics were balanced, except for race and programmed death-ligand 1 (PD-L1), although PD-L1 assessment was limited by incomplete reporting. Pembrolizumab plus belzutifan significantly improved DFS versus placebo (HR 0.55, 95% CI 0.45-0.69, P < 0.001). Despite immature OS data, the combination showed an OS benefit over placebo (HR 0.56, 95% CI 0.35-0.89, P = 0.014). CONCLUSIONS: Adjuvant pembrolizumab plus belzutifan showed a substantial DFS benefit compared with placebo. In a context where factors beyond efficacy demand robust evidence of clinical benefit, these findings reinforce the value of combined immune and hypoxia-inducible factor 2α inhibition.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.