Immunotherapy drug improves survival for people with kidney cancer in landmark clinical trial
For the first time in fifty years, researchers have shown that giving an immunotherapy drug to people with kidney cancer after surgery improves their overall survival in a phase 3 randomized, placebo-controlled trial. The trial was led by Dr Toni Choueiri at the Dana-Farber Cancer Institute and Professor Thomas Powles at Barts Cancer Institute, Queen Mary University of London.
Treatment with the immunotherapy drug pembrolizumab after surgery significantly prolonged overall survival in patients with, clear-cell renal-cell carcinoma (ccRCC; the most common subtype of kidney cancer), who are at high risk of their cancer coming back, according to an analysis of results from the KEYNOTE-564 study, published in the New England Journal of Medicine. Pembrolizumab was associated with a 38% reduction in risk of death compared with placebo.
"We can now tell our patients that pembrolizumab after surgery not only delays recurrences but also helps them live longer," said Dr Choueiri.
Investigators have been trying to find ways to reduce recurrences and prolong survival for this patient group since 1973, the date of the first randomized controlled trial of an adjuvant therapy. An adjuvant therapy is a medicine intended to enhance efficacy after primary treatment of the cancer, which in this case is surgery.
The KEYNOTE-564 trial was designed to evaluate adjuvant pembrolizumab following nephrectomy (removal of the cancerous kidney) within 12 weeks prior to randomization. The double-blind, phase 3 study, carried out at hundreds of sites internationally, enrolled 994 patients who were randomized 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.
"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 Dr Choueiri. "We showed pembrolizumab extends survival. It doesn't only delay recurrence."
In the first interim analysis of the KEYNOTE-564 study, Choueiri and colleagues reported that adjuvant pembrolizumab improved disease-free survival in patients with kidney cancer at high risk of relapse. Pembrolizumab was approved in 2021 as adjuvant treatment for patients with kidney cancer based on these KEYNOTE-564 results.
Prior to the approval of pembrolizumab, there was no widespread accepted standard of care for patients with ccRCC after treatment with surgery. Now, with adjuvant pembrolizumab as standard of care for this patient group, the team is investigating whether it can be improved by combining pembrolizumab with the HIF-2 inhibitor belzutifan.
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