Adjuvant pembrolizumab arises as new RCC option, but OS data await


Data from the phase 3 KEYNOTE-564 trial shared during the 2021 European Association of Urology (EAU) Congress showcased adjuvant pembrolizumab (Keytruda) as a potential new standard in renal cell carcinoma (RCC); however, investigators are still awaiting overall survival (OS) data to cement this role for the PD-1 inhibitor in the kidney cancer armamentarium.

Results shared in a webinar during the EAU meeting showed that at a median follow-up of approximately 24 months, adjuvant pembrolizumab induced a 32% reduction in the risk of disease recurrence or death compared with placebo (HR, 0.68; P = .0010).1 Per investigator assessment, the median disease-free survival (DFS) was not yet reached in either the pembrolizumab arm (n = 496) or the placebo arm (n = 498).

The OS data are immature, with 3.6% (n = 18) and 6.6% (n = 33) events occurring in the pembrolizumab and placebo arms, respectively. The median OS has not yet been reached in either arm but is trending favorably toward the PD-1 inhibitor (HR, 0.54; P = .0164); however, this has not cross the prespecified boundary of statistical significance. The estimated 2-year OS rates are 96.6% for pembrolizumab and 93.5% for placebo.

"This early data from the trial is very promising, with a clear reduction in the disease recurring in patients on pembrolizumab. There are signs as well that the drug may improve survival rates, but we can't be sure of that for another few years. We're hopeful that this trial, when complete, will provide a strong case for this drug to be approved for use by the medicines regulator,” Thomas Powles, MBBS, MRCP, MD, a coinvestigator on the study and director, Barts Cancer Institute, stated in a press release.2

The standard-of-care treatment for patients with locoregional RCC is surgery; however, nearly half of patients eventually experience disease recurrence. Currently, there is no standard adjuvant systemic therapy that is supported by high levels of evidence worldwide.

In the double-blind, multicenter, phase 3 KEYNOTE-564 study (NCT03142334), investigators explored pembrolizumab vs placebo following nephrectomy in patients with clear cell RCC. Specifically, patients’ disease had to meet criteria that categorized them as high risk for recurrence, which included: pT2, grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0; pT4, any grade, N0, M0; any pT, any grade, N-positive, M0; or M1 with no evidence of disease after surgery.

Patients must have undergone nephrectomy within 12 weeks prior to randomization, could not have previously received systemic treatment, had to have an ECOG performance status of 0 or 1, and a tissue sample must have been obtainable for PD-L1 assessment.

All patients were randomized 1:1 to receive pembrolizumab at 200 mg every 3 weeks or placebo every 3 weeks, both for approximately 1 year.

At 1 year, the estimated DFS rates were 85.7% and 76.2% with pembrolizumab and placebo, respectively. At 2 years, these rates were 77.3% and 68.1%, respectively.

Regarding safety, all-grade adverse effects (AEs) with pembrolizumab occurred in 96.3% of patients and in 91.1% of those on placebo; grade 3 to 5 AEs occurred in 32.4% and 17.7%, respectively. AEs led to death in 2 patients on pembrolizumab and in 1 patient on placebo.

The results from the KEYNOTE-564 trial were previously presented at the 2021 ASCO Annual Meeting.3 In a video interview with Urology Times during the ASCO meeting, Robert A. Figlin, MD, deputy director, Cedars-Sinai Cancer, shared his expert observations on important questions that still remain with KEYNOTE-564, despite the positive results of the trial. Among the topics Figlin addresses in the video are issues with the makeup of the study population.


1. Powles T. Pembrolizumab (pembro) vs. placebo as post nephrectomy adjuvant therapy for patients (pts) with renal cell carcinoma (RCC): randomized, double-blind, phase 3 KEYNOTE-564 study. Webinar at 36th Annual EAU Congress (virtual). July 8-12, 2021.

2. New use of old drug reduces risk of kidney cancer returning. Published online July 10, 2021. Accessed July 14, 2021.

3. Choueiri TK, Tomczak P, Park SH, et al. Pembrolizumab vs placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: randomized, double-blind, phase 3 KEYNOTE-564 study. J Clin Oncol. 2021;39(suppl 15):LBA5.

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