Adjuvant Pembrolizumab Dosing for Renal Cell Carcinoma
Administer pembrolizumab 200 mg intravenously every 3 weeks for 17 cycles (approximately 1 year) in the adjuvant setting for clear cell renal cell carcinoma. 1
Dosing Schedule
- Standard regimen: 200 mg IV every 3 weeks for up to 17 cycles 1
- Total duration: Approximately 12 months of treatment 1
- Timing after surgery: Must initiate within 12 weeks of nephrectomy 1
Patient Selection Criteria
Eligible patients include those with intermediate- or high-risk clear cell RCC defined as: 1
- Intermediate risk: pT2, grade 4 or sarcomatoid, N0 M0; OR pT3, any grade, N0 M0 1
- High risk: pT4, any grade, N0 M0; OR any pT, any grade, N+ M0 1
- M1 with no evidence of disease (NED): After complete resection of primary tumor plus soft tissue metastases within 1 year of nephrectomy 1
Evidence Supporting This Regimen
The KEYNOTE-564 trial established this dosing schedule with 994 patients randomized to pembrolizumab 200 mg every 3 weeks for 17 cycles versus placebo. 1
Key efficacy outcomes at extended follow-up (57.2 months median):
- Disease-free survival: HR 0.72 (95% CI 0.59-0.87) favoring pembrolizumab 2
- Overall survival: HR 0.62 (95% CI 0.44-0.87, P=0.005), with 48-month OS of 91.2% vs 86.0% for placebo 2
- 24-month DFS rate: 77.3% with pembrolizumab vs 68.1% with placebo 3
The ESMO guidelines specifically recommend this regimen as optional for intermediate- and high-risk patients after careful counseling about potential long-term adverse events. 1
Safety Profile
- Grade 3-5 adverse events: 32.4% with pembrolizumab vs 17.7% with placebo 3
- Treatment-related serious adverse events: 12% in the pembrolizumab group 4
- No treatment-related deaths occurred in the KEYNOTE-564 trial 3, 2
Important Clinical Caveats
Counsel patients extensively before initiating treatment because a substantial proportion of patients are cured by surgery alone and may receive unnecessary treatment with potential long-term toxicity. 1 The ESMO guidelines acknowledge that better biomarkers are urgently needed to identify which patients truly benefit. 1
For the M1 NED population specifically, adjuvant pembrolizumab can be offered after complete metastasectomy, but incomplete resection should not be performed. 1 If patients relapse within 1 year of nephrectomy, PD-1-based combination therapy becomes the standard of care rather than adjuvant monotherapy. 1
Do not reduce the pembrolizumab dose—the FDA label specifies no dose reduction is recommended; instead, withhold for severe (Grade 3) immune-mediated adverse reactions and permanently discontinue for Grade 4 reactions. 5