Treatment with Keytruda following surgery was associated with a significant reduction in the risk of disease recurrence or death compared with placebo in patients with clear cell renal cell carcinoma.
Data from the phase 3 KEYNOTE-564 trial demonstrated that treatment with Keytruda (pembrolizumab) following surgery was associated with a 32% reduction in the risk of disease recurrence or death compared with placebo in patients with clear cell renal cell carcinoma (RCC).
“Adjuvant (Keytruda) following surgery demonstrated a statistically significant and clinically meaningful improvement in (disease-free survival) versus placebo,” lead study author Dr. Toni K. Choueiri, director of the Lank Center for Genitourinary Oncology and director of the Kidney Cancer Center at Dana-Farber Cancer Institute in Boston, said during a presentation of the data prior to the 2021 ASCO Annual Meeting. “KEYNOTE-564 is the first positive phase 3 study of an adjuvant immunotherapy for patients with RCC. (Keytruda) is a potential new standard of care for patients with RCC in the adjuvant setting.”
The standard-of-care treatment for patients with locoregional RCC is surgery; however, nearly half of patients eventually experience disease recurrence. Currently, there is no standard adjuvant (treatment following surgery) systemic therapy that is supported by high levels of evidence worldwide.
In the double-blind, multicenter, phase 3 KEYNOTE-564 study, investigators explored Keytruda versus placebo following nephrectomy (surgical removal of one or both kidneys) in patients with clear cell RCC. Specifically, patients’ disease had to meet criteria that categorized them as high risk for recurrence.
Patients must have undergone nephrectomy within 12 weeks prior to randomization and could not have previously received systemic treatment.
All patients were randomized to receive either 200 milligrams of Keytruda every three weeks or placebo every three weeks, both for approximately one year. Measuring disease-free survival (the time after treatment without signs of cancer) was the main goal of the study. Other goals included assessing overall survival (time that a patient with cancer is still alive) and safety.
At one year, the estimated disease-free survival rates were 85.7% and 76.2% with Keytruda and placebo, respectively. At two years, these rates were 77.3% and 68.1%, respectively.
The overall survival data are immature, with 18 and 33 events occurring in the Keytruda and placebo groups, respectively.
Regarding safety, side effects occurred in 96.3% of patients receiving Keytruda and 91.1% of patients receiving placebo; Serious or severe side effects occurred in 32.4% and 17.7%, respectively. Side effects led to death in two patients in the Keytruda group and in one patient in the placebo group.
Treatment-related side effects occurred in 79.1% and 53.4% of Keytruda- and placebo-treated patients, respectively. A total 18.9% of patients in the Keytruda group experienced serious or severe treatment-related side effects vs 1.2% of those receiving placebo. Of note, no treatment-related side effects led to death in either treatment group. Overall, the safety profile was consistent with prior data regarding Keytruda.
“KEYNOTE-564 is the first phase 3 trial to show improved (disease-free survival) from the addition of an immune checkpoint inhibitor in the adjuvant setting for clear cell RCC, which is the most common type of kidney cancer,” said ASCO’s Executive Vice President Dr. Julie Gralow during the press briefing. “Despite surgery, recurrence is common in clear cell RCC, and if it does recur, there are limited curative treatment options. The results of the KEYNOTE-564 trial support consideration of (Keytruda) as a potential new standard of care in the adjuvant setting to reduce disease recurrence in certain patients with kidney cancer.”
Keytruda is currently approved for use in combination with Inlyta (axitinib) for the first-line treatment of patients with advanced RCC.
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