Institute of Genetics and Cancer

Adjuvant pembrolizumab improves survival in high-risk clear cell renal cell cancer

Recent results from the KEYNOTE-564 trial, an international study with its UK component led from Edinburgh, support adjuvant pembrolizumab as a standard of care after surgery for patients with clear cell renal cell cancer (kidney cancer): April 2024

Pembrolizumab is a humanized antibody which targets the programmed cell death protein 1 (PD-1) receptor of T cells, a type of white blood cells constituting an essential part of the immune system. When functioning properly, T cells become activated and can attack tumour cells but some tumours can evade the immune system through the PD-1 pathway. The PDL1 and PDL2 ligand proteins on tumour cells can bind with PD-1 receptors on T cells to inactivate the T cells. Pembrolizumab binds to the PD-1 receptor and blocks its interaction with PDL1 and PDL2, which helps restore the immune response.

Pembrolizumab (Keytruda) prevents PD‑L1 and PD‑L2 ligand proteins on tumour cells from binding with PD⁠-⁠1 receptors on T cells
Pembrolizumab (Keytruda) prevents PD‑L1 and PD‑L2 ligand proteins on tumour cells from binding with PD⁠-⁠1 receptors on T cells to inactivate the T cells. [Figure by Dr A. Welman]

Pembrolizumab was approved in 2021 for adjuvant treatment of patients with renal-cell carcinoma (kidney cancer) and it has already become the standard of care. This was possible because of positive results from an interim analysis of the KEYNOTE-564 study, a randomised, double-blind, phase III international clinical trial, which showed that the trial met its primary endpoint of reducing the risk of relapse. However, further data from the study were eagerly awaited by patients and the oncology community, to know if this resulted in patients living longer.

These new data were recently published in the New England Journal of Medicine in an article titled “Overall survival with adjuvant pembrolizumab in renal-cell carcinoma”. The investigators, including Edinburgh’s Dr Stefan Symeonides as the trial’s UK Chief Investigator, presented overall survival results from the third prespecified interim analysis (with a median follow-up of 57.2 months). The results showed that for patients with clear cell renal cell cancer (ccRCC) at intermediate-high or high risk of recurrence after surgery, adjuvant pembrolizumab improved both disease-free survival, and now overall survival, compared with placebo. The pembrolizumab group had a 38% reduced risk of death versus placebo, consistent with and extending results from a prior analysis at 24 months. The published study provides further support for adjuvant pembrolizumab as a standard of care after surgery for patients with ccRCC who are at higher risk of recurrence. In the 50 years since the first randomised trial of adjuvant therapy in renal cell carcinoma, nearly 20 studies have look at this question; KEYNOTE-564 represents the first such study to show an overall survival benefit for patients.

Related Links

Publication in the New England Journal of Medicine, “Overall survival with adjuvant pembrolizumab in renal-cell carcinoma”: https://www.nejm.org/doi/full/10.1056/NEJMoa2312695

Information about KEYNOTE-564 clinical trial: https://clinicaltrials.gov/ct2/show/NCT03142334

Dr Stefan Symeonides research profile: https://www.ed.ac.uk/cancer-centre/research/symeonides-group

Information about kidney cancer: https://www.cancerresearchuk.org/about-cancer/kidney-cancer

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