Postsurgical Keytruda Improves Survival in Clear Cell Kidney Cancer

Researchers from a phase 3 trial demonstrated that certain patients with clear cell kidney cancer may benefit form postsurgical Keytruda.

Postsurgical immunotherapy significantly improved survival in patients with clear-cell renal cell carcinoma (ccRCC) whose disease is at a high risk of recurrence, according to recent findings from the KEYNOTE-564 clinical trial. More specifically, researchers from the study observed a 38% reduction in the risk of death for patients who were given Keytruda (pembrolizumab) compared to those given a placebo.

Study findings were published in the New England Journal of Medicine.

“We can now tell our patients that [Keytruda] after surgery not only delays recurrences but also helps them live longer,” lead study author, Dr. Toni Choueiri, of the Dana-Farber Cancer Institute, said in a press release.

KEYNOTE-564 was a phase 3 trial that included 994 patients with ccRCC who underwent nephrectomy (surgical removal of the kidney). After their surgery, patients were randomly assigned to receive either Keytruda or a placebo for every three weeks for approximately a year.

To be eligible for the trial, patients had to have ccRCC that was at an intermediate or high risk of recurrence. While surgery is intended to be curative for this patient population, approximately 30% to 50% experience a recurrence — which often includes metastatic disease or cancer that spreads — after surgery.

At a follow-up of 57.2 months, Keytruda led to better overall survival (time from treatment until death of any cause) compared to placebo. This survival benefit was observed across multiple disease subgroups, including different disease stages, risk stratification, immunological biomarkers and other characteristics.

At 48 months, 91.2% of patients in the Keytruda group were still alive, compared with 86% of patients in the placebo group, according to the study findings.

For decades, researchers have been searching for an adjuvant (post-surgical) treatment to improve outcomes for patients with ccRCC. KEYNOTE-564 was the first study to prove that the drug may improve outcomes in this space, according to the press release.

“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 [Keytruda] extends survival. It doesn’t only delay recurrence.”

Keytruda is a drug called a checkpoint inhibitor that works by blocking a certain protein on cancer cell surfaces that helps it hide from the immune system. In doing so, the body can then find and attack the cancer. The drug was initially approved in the kidney cancer space in 2021 for the adjuvant treatment of intermediate-high or high-risk renal cell carcinoma.

The Keytruda group, however, had a higher rate of serious side effects of any cause compared to the placebo group, at 20.7% versus 11.5%, respectively. The rate of grade 3 or 4 side effects was 18.6% and 1.2%, respectively, and there were no deaths related to Keytruda therapy.

Ultimately, the researchers concluded, “Adjuvant [Keytruda] was associated with a significant and clinically meaningful improvement in overall survival, as compared with placebo, among participants with clear-cell renal-cell carcinoma at increased risk for recurrence after surgery.”

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