Pembrolizumab Improves OS in RCC Following Nephrectomy


In the KEYNOTE-564 trial, patients with renal cell carcinoma who had a nephrectomy achieved improved overall survival rates vs placebo when treated with adjuvant pembrolizumab.

Illustration of kidney cancer

Illustration of kidney cancer

Pembrolizumab (Keytruda) demonstrated significant improvements in overall survival (OS) compared with placebo when used as an adjuvant therapy in the treatment of patients with renal cell carcinoma (RCC) at intermediate-high- or high-risk of recurrence following nephrectomy, according to findings from the KEYNOTE-564 trial (NCT03142334) released by Merck, pembrolizumab’s manufacturer.1

Pembrolizumab showed statistically significant and clinically meaningful improvement in OS, and the results will be submitted to regulatory authorities and presented at an upcoming medical meeting. OS is the key secondary end point in the KEYNOTE-564 trial, and, according to Merck, this is the second study of pembrolizumab in earlier stages of cancer to show OS benefits. OS data from the KEYNOTE-671 in stages II-IIIB non–small cell lung cancer was recently presented at the European Society for Medical Oncology Congress 2023.

“These new results from KEYNOTE-564 are notable and mark the first time a therapy has demonstrated a statistically significant survival benefit compared to placebo in patients with RCC at a higher risk of recurrence following surgery, building on the positive disease-free survival findings from this study that led to approvals around the world for this [pembrolizumab]-based regimen,” said Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, in a press release.1

About KEYNOTE-564

KEYNOTE-564 is a phase 3, randomized, double-blind, placebo-controlled clinical trial of pembrolizumab as monotherapy in adjuvant treatment of RCC post-nephrectomy. The trial has an enrollment of 994 patients broken into 2 arms. Patients in the experimental arm receive 200 mg of intravenous pembrolizumab on day 1 of a 3-week cycle for up to 17 cycles or approximately 1 year. Patients in the placebo arm receive a saline solution at the same timing as the experimental arm.2

KEYNOTE-564 previously met its primary end point of disease-free survival. Risk of disease recurrence or death was reduced by 32% (HR, 0.68; 95% CI, 0.53-0.87; P =.0010) compared with placebo.1 Additional secondary end points include number of patients who experienced an adverse event (AE), number of patients who discontinued the study drug due to an AE, first local disease recurrence-specific survival, second disease recurrence-specific survival, and event-free survival.2

Pembrolizumab’s safety profile in this study is consistent with what has been observed in previous trials, and no new safety signals have been noted.1

Patients were not eligible for study participation if they had major surgery other than nephrectomy within 12 weeks of randomization, received prior radiotherapy for RCC, pre-existing brain or bone metastases, immunodeficiency diagnosis, active autoimmune disease that required systemic treatment within 2 years of randomization, a history of dialysis, known hepatitis B or C infection, history of active tuberculosis, or prior solid organ transplant, among other criteria.

The trial has an estimated completion date of December 2025.2

1. Keytruda (pembrolizumab) significantly improved overall survival (OS) versus placebo as adjuvant therapy for certain patients with renal cell carcinoma (RCC) following nephrectomy. News release. Merck. November 1, 2023. Accessed November 1, 2023.
2. Safety and efficacy study of pembrolizumab (MK-3475) as monotherapy in the adjuvant treatment of renal cell carcinoma post nephrectomy (MK-3475-564/KEYNOTE-564). Updated June 29, 2023. Accessed November 1, 2023.
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