KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery
One year of pembrolizumab after surgery for high-risk kidney cancer reduced relapses by about a third and, in later follow-up, became the first adjuvant treatment to help kidney cancer patients live longer.
Double-blind, placebo-controlled phase 3 trial of 994 patients with clear-cell renal cell carcinoma at intermediate-high or high risk of recurrence after nephrectomy, or with resected metastatic disease (M1 NED), randomised to one year of pembrolizumab or placebo. Primary endpoint was disease-free survival.
24-month DFS was 77.3% vs 68.1% (HR 0.68). The 2024 overall survival analysis showed HR 0.62 with 48-month OS 91.2% vs 86.0%. It was the first adjuvant therapy in kidney cancer to improve survival, after decades of negative trials with cytokines and VEGF inhibitors, and it stands alone: three other adjuvant checkpoint inhibitor trials (IMmotion010, CheckMate 914, PROSPER) were negative.
- 24-month disease-free survival 77.3% vs 68.1%; HR 0.68 (95% CI 0.53-0.87).
- Overall survival (NEJM 2024): HR 0.62 (95% CI 0.44-0.87); 48-month OS 91.2% vs 86.0%.
- Largest DFS benefit in the small M1 NED group (HR 0.28) and in sarcomatoid tumours.
- Grade 3 or higher adverse events 32.4% vs 17.7%; about 21% discontinued pembrolizumab for adverse events.
- Endocrine immune-related events (hypothyroidism, adrenal insufficiency) were the most frequent lasting toxicities.
Patients whose kidney cancer has been removed but who are at high risk of recurrence (large or high-grade tumours, node involvement, or resected metastases) can now be offered a year of pembrolizumab, which increases the chance of being alive and cancer-free several years later. Roughly nine patients need treatment to prevent one recurrence at two years, and some will have permanent side effects, so shared decision-making matters. Why pembrolizumab succeeded where similar drugs failed is not fully understood.
- The three other adjuvant checkpoint inhibitor trials in kidney cancer were negative, and the reasons (drug, population, chance) are debated.
- Absolute DFS benefit of about 9 points; most patients treated would not have relapsed anyway.
- The trial predated widespread use of immunotherapy at relapse in the control arm during the early years, which may exaggerate the OS effect relative to current practice.
- Non-clear-cell histology was excluded.
Pages like this
not linked directly; found by shared links- Key paperCLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer
Shares Toni K. Choueiri, Merck & Co. (MSD), Overall survival (OS), Renal cell carcinoma.
- TrialKEYNOTE-564
Shares Toni K. Choueiri, Neoadjuvant / adjuvant / perioperative, Renal cell carcinoma, Pembrolizumab.
- IdeaPredict immune side-effects before they happen and pre-empt them
Shares Immune-related adverse events (irAEs), Toxicity and quality of life are undervalued, Pembrolizumab, Immune checkpoint inhibitors.
- Key paperKEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation
Shares Immune-related adverse events (irAEs), Merck & Co. (MSD), Overall survival (OS), PD-1.
- Key paperKEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer
Shares Immune-related adverse events (irAEs), Merck & Co. (MSD), Neoadjuvant / adjuvant / perioperative, Dormant cells and minimal residual disease.
- IdeaTreat immunotherapy side-effects without wiping out the response
Shares Immune-related adverse events (irAEs), Renal cell carcinoma, Toxicity and quality of life are undervalued, Immune checkpoint inhibitors.
- TrialKEYNOTE-426
Shares Jae Lyun Lee, Renal cell carcinoma, Pembrolizumab.
- Key paperRELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma
Shares Immune-related adverse events (irAEs), Overall survival (OS), Toxicity and quality of life are undervalued, PD-1.