Clinical trialPhase 3Kidney cancer

Adjuvant pembrolizumab for the treatment of clear cell renal cell carcinoma: five-year results from the phase III KEYNOTE-564 study

Ann Oncol · 2026994 patients (496 pembrolizumab, 498 placebo)

Haas NB, Powles TB, Tomczak P, Park SH, Venugopal B, Symeonides SN, et al. Ann Oncol. 2026

Study type: Clinical trial
Study name: KEYNOTE-564
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial (fourth prespecified interim analysis)
Sample size: 994 patients (496 pembrolizumab, 498 placebo)
Source: Ann Oncol · 2026
Trial registration: NCT03142334

In plain words

In patients with kidney cancer at high risk of coming back, one year of immunotherapy with pembrolizumab after surgery still lowered the chance of the cancer returning and of death after about 6 years of follow-up: 87.7% versus 82.3% of patients were alive after 5 years.

Key results

60.9% vs 52.2%

5-year disease-free survival

HR 0.71 (0.59–0.86); median not reached vs 68 months

87.7% vs 82.3%

5-year overall survival

HR 0.66 (0.48–0.90)

70 months

Median time from randomisation to data cut-off

Range 60–87 months

Drugs in this study:Pembrolizumab (Keytruda)

Dose and schedule cards

Adjuvant pembrolizumab (KEYNOTE-564)

RCC with a clear-cell component after nephrectomy at intermediate-high risk (pT2 grade 4 or sarcomatoid, or pT3) or high risk (pT4 or N+), or M1 NED after nephrectomy and complete resection of metastasesOn the page “Kidney cancer” · Adjuvant therapy regimens after nephrectomy

Drug	Dose	Route	Schedule
Pembrolizumab	200 mg (or 400 mg)	IV, 30-minute infusion	Day 1 every 3 weeks (400 mg dose: every 6 weeks)

Cycle length: Every 21 days (or every 42 days with the 400 mg dose)
Duration: Up to 12 months, or until recurrence or unacceptable toxicity (in KEYNOTE-564: 200 mg every 3 weeks for up to 17 cycles)

Dose and duration per the FDA label and the trial. The EAU recommends starting treatment preferably within 12 to 16 weeks after nephrectomy, after repeat imaging.

On the page “Kidney cancer” · Adjuvant therapy regimens after nephrectomy

Adjuvant pembrolizumab

After nephrectomy at intermediate-high or high risk of recurrenceCycle length: Every 3 weeksOn the page “Immunotherapy regimens in kidney cancer: pembrolizumab-axitinib, nivolumab-ipilimumab and adjuvant pembrolizumab”

After nephrectomy at intermediate-high or high risk of recurrence

Drug	Dose	Route	Schedule
Pembrolizumab	200 mg (or 400 every 6 weeks)	IV	Every 3 weeks

Cycle length: Every 3 weeks
Duration: Up to 17 doses (about one year)

As in KEYNOTE-564.

Dose source:.

On the page “Immunotherapy regimens in kidney cancer: pembrolizumab-axitinib, nivolumab-ipilimumab and adjuvant pembrolizumab”

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Pembrolizumab

Pembrolizumab 200 mg IV on day 1 of each 3-week cycle for up to 17 cycles (about 1 year), or until recurrence, unacceptable toxicity or meeting treatment discontinuation criteria.

2Placebo

Placebo (saline) IV every 3 weeks on the same schedule, for up to 17 cycles (about 1 year).

Source of the regimen details: Abstract of the paper (PubMed), abstract of the main report (NEJM 2021) and ClinicalTrials.gov NCT03142334

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with renal cell carcinoma with a clear cell component (with or without sarcomatoid features) after partial or radical nephrectomy with negative margins, without previous systemic therapy, with ECOG 0 or 1, and in one of these groups: intermediate-high risk (pT2 grade 4 or sarcomatoid, N0 M0; or pT3 any grade, N0 M0), high risk (pT4 N0 M0; or any pT with N+‎ M0), or M1 NED (a solitary soft-tissue metastasis completely resected at the time of nephrectomy or within 1 year after it). Surgery 28 days or more before consent and no more than 12 weeks before randomisation; no evidence of disease on imaging of the brain, chest, abdomen and pelvis or on bone scan; patients with previous brain or bone metastases, residual renal vein/vena cava thrombus, previous radiotherapy or active autoimmune disease were excluded (ClinicalTrials.gov NCT03142334).

Endpoints

Primary: investigator-assessed disease-free survival; key secondary: overall survival; secondary: safety.

Safety and side effects

According to this report, safety was nearly unchanged from the previous analysis. In the main report (NEJM 2021), grade 3 or higher adverse events of any cause occurred in 32.4% of pembrolizumab patients and 17.7% of placebo patients, and no pembrolizumab-related deaths were reported.

Clinical significance and place in guidelines

This report confirms the durability of the overall survival benefit of adjuvant pembrolizumab; the EAU guideline recommends it with a strong recommendation for high-risk ccRCC patients.

Limitations

These are interim analysis results and safety details are not given in the abstract; some patients are overtreated with pembrolizumab.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.