Background
Phase III RCT (N=994) of clear-cell RCC after nephrectomy at intermediate-high or high risk of recurrence, or M1 with no evidence of disease (M1 NED) after resection of metastases.
Interventions and follow up
Arm A: Pembrolizumab 200mg IV q3wk x17 cycles (~1yr)
Arm B: Placebo
Primary endpoint: DFS
Median follow-up: 24.1mo
Arm B: Placebo
Primary endpoint: DFS
Median follow-up: 24.1mo
Results
mDFS (A vs B): not reached in either arm; HR 0.68, 95% CI 0.53-0.87, P=.001
2-yr DFS: 77.3% vs 68.1%
OS: immature at primary analysis (early HR favored pembrolizumab; subsequent updates reported a statistically significant OS benefit)
2-yr DFS: 77.3% vs 68.1%
OS: immature at primary analysis (early HR favored pembrolizumab; subsequent updates reported a statistically significant OS benefit)
Adverse events
Grade 3-5 all-cause AEs (A vs B): 32.4% (158 pts) vs 17.7% (88 pts)
Immune-mediated: hypothyroidism and hyperthyroidism most common; grade 3-4 immune-mediated AEs in a minority, no treatment-related deaths
Immune-mediated: hypothyroidism and hyperthyroidism most common; grade 3-4 immune-mediated AEs in a minority, no treatment-related deaths
Conclusions
Adjuvant pembrolizumab significantly improved DFS versus placebo in intermediate-high/high-risk or M1 NED clear-cell RCC after nephrectomy.
Key Limitations
Initial report from a conference abstract with limited follow-up; OS immature at the time of this dataset; clear-cell histology only.
Clinical Context
FDA approved adjuvant pembrolizumab (Nov 2021) for RCC at increased recurrence risk after nephrectomy. First adjuvant therapy in RCC to show an OS benefit on later follow-up; preferred adjuvant option per ASCO/ESMO. Contrasts with negative IMmotion010 (atezolizumab) and CheckMate 914 (nivo/ipi).