Treatment with the checkpoint inhibitor pembrolizumab (Keytruda) following surgery significantly extended disease-free survival (DFS) in patients with high-risk, clear-cell renal-cell carcinoma (RCC) compared with placebo, according to the results of the KEYNOTE-564 clinical trial. These findings were reported during a plenary session of the ASCO 2021 virtual annual meeting.
“KEYNOTE-564 is the first phase 3 study to show an improvement in DFS with adjuvant immunotherapy in patients with high-risk, fully-resected, clear-cell RCC, the most common type of kidney cancer,” said Toni K. Choueiri, MD, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA. “The improvement in DFS was statistically significant and clinically meaningful. Pembrolizumab may provide a promising treatment for patients for whom there are few therapy options. KEYNOTE-564’s DFS supports pembrolizumab as a potential new standard of care in RCC.”
KEYNOTE-564 was a phase 3, international, multicenter trial that included 994 patients with histologically confirmed, high-risk, clear-cell RCC who had undergone partial nephrectomy at least 12 weeks prior to randomization. No previous systemic therapy was allowed, and patients were randomized in a 1:1 ratio to receive adjuvant pembrolizumab 200 mg every 3 weeks for up to 17 cycles or placebo. The primary end point was DFS per investigator’s assessment; secondary end points included overall survival and safety.
At a median follow-up of 24.1 months, the primary end point was met, and median DFS was not reached in either arm. Adjuvant pembrolizumab reduced the risk for recurrence or death by 32% compared with placebo (one-sided P = .0010).
The 12-month DFS rate was 85.7% with pembrolizumab versus 76.2% with placebo. At month 24, the rate of DFS was 77.3% versus 68.1%, respectively.
At 24 months, the estimated OS was 96.6% in the pembrolizumab arm and 93.5% in the placebo arm, representing a 46% reduction for pembrolizumab. Median OS was not reached in either arm. Additional follow-up for this key secondary end point is planned. In total, 51 deaths occurred, 18 in the pembrolizumab arm and 33 in the placebo arm.
“I would argue that these data are practice-changing and represent a paradigm shift. This is the first positive phase 3 study of adjuvant immunotherapy in RCC. The prolongation of DFS represents clinical benefit. Given the magnitude of benefit and limited toxicity, adjuvant pembrolizumab represents a quantum leap forward for our patients and provides a new option for patients with clear-cell RCC,” said formal discussant Rana R. McKay, MD, Associate Clinical Professor, Urology, University of California San Diego.
“Despite surgery, recurrence is common in clear-cell RCC, and should it recur, there are limited curative treatments for patients. Given the success of pembrolizumab in the KEYNOTE-564 trial, this population may soon have a new standard of care,” said Julie R. Gralow, MD, FACP, FASCO, ASCO Chief Medical Officer and Executive Vice President, at a premeeting press conference.
Adverse events (AEs) of any grade were reported in 96.3% of patients in the pembrolizumab arm versus 91.1% of those in the placebo arm. Grade 3 to 5 AEs occurred in 32.4% versus 17.7% of patients, respectively. A total of 2 deaths attributed to all-cause AEs were reported in the pembrolizumab arm versus 1 in the placebo arm.
Treatment-related AEs were observed in 79.1% of the pembrolizumab arm versus 53.4% of the placebo arm. Grade 3 to 5 treatment-related AEs occurred in 18.9% versus 1.2%, respectively. No deaths due to treatment-related AEs were reported.
“Safety results were in line with expectations, and there were no new safety signals with pembrolizumab,” said Dr Choueiri.