For the first time in 50 years, a phase 3 randomised, placebo-controlled trial found that an adjuvant therapy improved overall survival in kidney cancer patients.

According to a review of keynote-564 research findings, treating patients with clear-cell renal-cell carcinoma (ccRCC) at high risk for recurrence with pembrolizumab, an immunotherapy medication, following surgery significantly improved overall survival.

Pembrolizumab reduced the risk of death by 38% compared to placebo. "We can now tell our patients that pembrolizumab after surgery not only delays recurrences but also helps them live longer," said the study's lead investigator Toni Choueiri, MD, of Dana-Farber Cancer Institute.

Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber, is the first author of the study published in the New England Journal of Medicine. Choueiri previously presented the findings at the American Society of Clinical Oncology (ASCO) Genitourinary Cancer Symposium on January 27, 2024.

The KEYNOTE-564 trial was designed to evaluate adjuvant pembrolizumab following nephrectomy (removal of the cancerous kidney) within 12 weeks before randomisation.

The double-blind, phase 3 study, carried out at hundreds of sites internationally, enrolled 994 patients who were randomised to pembrolizumab once every three weeks for about a year, or a placebo.

Pembrolizumab targets a molecular pathway that cancer cells commandeer to evade attack by the body's immune system. By blocking this "checkpoint" pathway, the drug helps free the immune system's army of T cells to combat tumours.

For inclusion in the trial, patients had to have a clear-cell component to their tumour and be at intermediate or high risk of recurrence. Some patients with resected metastases after nephrectomy were also eligible.

For patients with ccRCC, surgery is intended to be curative. However, between 30 and 50% of patients can experience recurrence after surgery. Recurrences often result in metastatic disease, which is usually incurable.

Investigators have been trying to find ways to reduce recurrences and prolong survival for this patient group since 1973, the date of the first randomised controlled trial of adjuvant therapy. An adjuvant therapy is a medicine intended to enhance efficacy after primary treatment of the cancer, which in this case is surgery.

"Since 1973, more than 12,000 patients with kidney cancer participated in adjuvant studies versus a control arm and none of the studies showed the experimental arm extends lives until now with the KEYNOTE-564 study," says Choueiri. "We showed pembrolizumab extends survival. It doesn't only delay recurrence."