Clinical trialPhase 3Kidney cancer

Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma

N Engl J Med · 2021994 patients (496 in the pembrolizumab group and 498 in the placebo group)

Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, et al. N Engl J Med. 2021. 385:683-694

A newer report of this study has been published: Adjuvant pembrolizumab for the treatment of clear cell renal cell carcinoma: five-year results from the phase III KEYNOTE-564 study (2026)

Study type: Clinical trial
Study name: KEYNOTE-564
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial (1:1 randomisation ratio)
Sample size: 994 patients (496 in the pembrolizumab group and 498 in the placebo group)
Source: N Engl J Med · 2021
Trial registration: NCT03142334

In plain words

In this study, patients who had had surgery for kidney cancer (of the clear cell type) and had a high risk of the disease coming back were given either the immunotherapy drug pembrolizumab or a placebo for about a year after surgery. Patients who received pembrolizumab stayed free of the disease for longer. Severe side effects were more common in the pembrolizumab group, but no deaths caused by the drug were reported.

Key results

24.1 months

Follow-up (median time from randomisation to data cut-off)

At the prespecified interim analysis

77.3% vs 68.1% (pembrolizumab vs placebo)

Disease-free survival at 24 months

P = 0.002 (two-sided)

0.68

Hazard ratio for recurrence or death

95% CI 0.53–0.87

96.6% vs 93.5% (pembrolizumab vs placebo)

Estimated percentage of patients alive at 24 months

Hazard ratio for death 0.54 (95% CI 0.30–0.96)

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 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 endpoint: disease-free survival by investigator assessment. Overall survival was the key secondary endpoint. Safety was also a secondary endpoint.

Safety and side effects

Grade 3 or higher adverse events of any cause occurred in 32.4% of patients in the pembrolizumab group and 17.7% of patients in the placebo group. No treatment-related deaths with pembrolizumab were reported.

Clinical significance and place in guidelines

This trial showed that adjuvant pembrolizumab after nephrectomy in high-risk patients with clear cell renal cell carcinoma significantly improves disease-free survival compared with placebo and may be an option for adjuvant treatment in these patients. Given the increase in grade 3 or higher adverse events, patient selection and discussion of adverse effects are essential. Regulatory approval status and clinical guideline recommendations should be checked separately, as they are not mentioned in the abstract.

Limitations

The results come from an interim analysis with a median follow-up of 24.1 months. The primary endpoint was investigator-assessed. Overall survival data were still immature in this analysis (based on the small number of events and the relatively wide confidence interval). The trial was funded by the manufacturer.

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.