A roundtable discussion led by Thomas Hutson highlighted the growing role of adjuvant Pembrolizumab in high-risk clear cell renal cell carcinoma (ccRCC) following nephrectomy, based on results from the phase 3 KEYNOTE-564 trial.
The study compared one year of pembrolizumab versus placebo in patients with resected high-risk disease and showed a 29% reduction in recurrence or death risk (HR 0.71) and a 34% reduction in death risk at five years (HR 0.66). These findings have led to major guideline updates, with NCCN Guidelines (v3.2025) now listing pembrolizumab as a Category 1 recommendation for Stage III disease, while sunitinib has been removed from this setting.
Experts noted that benefit is greatest in patients with M1 NED status, with an estimated 70% risk reduction. Treatment is ideally started within 90 days after surgery, as delayed initiation appears to reduce benefit. Management after relapse depends on timing, with early progression favoring TKIs and later relapse allowing immunotherapy rechallenge.