ASCO26: Toni Choueiri, MD, KEYNOTE-654

Data highlights limitations of ctDNA assay used to predict outcomes in participants with renal cell carcinoma treated with adjuvant pembrolizumab in the KEYNOTE-564 trial. Dana-Farber Cancer Institute's Dr. Toni Choueiri explains that ctDNA+ was associated with worse disease-free outcomes, but sensitivity was low.

July 1, 2026

Dana-Farber

Overview

The ctDNA assay used in the KEYNOTE-564 trial showed low sensitivity in predicting outcomes for renal cell carcinoma patients treated with adjuvant pembrolizumab. ctDNA positivity correlated with worse disease-free survival.

Background

The assessment of circulating tumor DNA (ctDNA) has emerged as a potential biomarker for predicting cancer outcomes. In the context of renal cell carcinoma (RCC), understanding the efficacy of ctDNA assays is important for patient management, particularly regarding adjuvant therapies like pembrolizumab.

Data Highlights

No numerical data available in the source material.

Key Findings

ctDNA positivity was associated with worse disease-free survival in both treatment arms of the KEYNOTE-564 trial.
Baseline ctDNA was detectable in only 5.4% (16-plex) and 8.2% (64-plex) of patients.
The ctDNA assays demonstrated high specificity but low sensitivity for recurrence risk.
Pembrolizumab showed benefit regardless of baseline ctDNA status.
On-treatment ctDNA clearance occurred more frequently with pembrolizumab compared to placebo.
Current exome-based ctDNA assays do not support routine patient selection for adjuvant pembrolizumab in high-risk RCC.

Clinical Implications

The low sensitivity and positivity rates of ctDNA assays indicate limitations in their use for guiding adjuvant treatment decisions in RCC.

Conclusion

The findings from the KEYNOTE-564 trial indicate that ctDNA may correlate with disease outcomes, but its limitations should be considered in clinical contexts.