KEYNOTE-564: Navigating Adjuvant Pembrolizumab in RCC

In an interview at the 2026 ESMO Congress, Toni Choueiri, MD, of Dana-Farber Cancer Institute, discusses the clinical implications of the final 7-year analysis of the phase 3 KEYNOTE-564 trial (NCT03142334), which evaluated adjuvant pembrolizumab (Keytruda) in patients with clear cell renal cell carcinoma (RCC) following nephrectomy.

Choueiri reviews subgroup findings by risk category and sarcomatoid features, emphasizing that the benefit of adjuvant pembrolizumab was consistent across the prespecified subgroups. Although patients with sarcomatoid features or M1 no evidence of disease (M1 NED) status had worse prognoses in the control arm, no particular subgroup demonstrated a greater benefit from pembrolizumab. These findings support considering adjuvant treatment across eligible patient populations rather than limiting referrals based on individual risk features.

He also discusses the role of pembrolizumab in reducing the risk of disease relapse and distant metastases following surgery, while highlighting important considerations when counseling patients about adjuvant therapy. Although most treatment-related adverse events were low grade, some patients experienced higher-grade toxicities. Choueiri underscores the potential for overtreatment, noting that surgery alone can still be curative, even among patients with high-risk disease, including those with M1 NED status.

Looking ahead, Choueiri highlights the need for biomarkers to better identify patients most likely to benefit from adjuvant treatment. He discusses circulating tumor DNA (ctDNA) and kidney injury molecule-1 (KIM-1) as potential tools that could help guide treatment selection and support a more individualized approach to adjuvant therapy in RCC.