"[This is] the first time ever since we started conducting randomized phase 3 studies in the adjuvant setting of kidney cancer that we see an overall survival benefit," says Toni K. Choueiri, MD.
In this video, Toni K. Choueiri, MD, highlights the key findings from the study, “Overall survival results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab versus placebo for the treatment of clear cell renal cell carcinoma (ccRCC),” which were presented at the 2024 ASCO Genitourinary Cancers Symposium in San Francisco, California. Choueiri is the director of the Lack Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts.
KEYNOTE-564 (NCT03142334) is a randomized phase 3 study in patients with high risk of recurrence after nephrectomy, patients with kidney cancer. The initial results of the study were presented as part of the ASCO plenary session in 2021. The study met its primary end point of disease-free survival. One year of pembrolizumab extended disease-free survival compared to 1 year of placebo. This was a study in patients with confirmed clear cell RCC, who didn't have systemic therapies, who ended up being T2 grade 4, T3, N+ or M1 NED within in a year. Patients got a year of pembrolizumab or a year of placebo. The primary end point was disease-free survival. Now what we did 3 years later, at GU Cancers Symposium in San Francisco in January 2024, we presented the third interim analysis of the key secondary end point of overall survival. We're happy to say that the overall survival was met. Hazard ratio was .62, corresponding to a 38% decrease in the risk of death. [This is] the first time ever since we started conducting randomized phase 3 studies in the adjuvant setting of kidney cancer that we see an overall survival benefit.
We did extra analysis from the study to look at updated disease-free survival, and this also was statistically significant; it remained. We looked at subgroup analysis for overall survival, and the benefit was consistent. We did an analysis that looked at updated toxicity. The first time toxicity was after 30 months follow-up. Now we have a 57-month follow-up, and they're practically the same. We conclude that the survival benefit was seen across key subgroups. It further supports pembrolizumab as the standard of care in disease setting. As next step, we already have started accruing patients to the next trial by the name, LITESPARK-022, which the standard is not placebo anymore. It's a year of pembrolizumab. On top of that, we add the HIF-2 inhibitor belzutifan. [It has] largely the same eligibility criteria. The study is happening. [It's an] international study, also led by Dana Farber, and it's open at Dana Farber Cancer Institute.
This transcription has been edited for clarity.