Immunotherapy with pembrolizumab after surgery reduces disease recurrence in patients with clear-cell renal-cell carcinoma (ccRCC), the most common type of kidney cancer, according to the phase-3 KEYNOTE-564 study. "Adjuvant pembrolizumab following surgery demonstrated a statistically significant and clinically meaningful improvement in disease-free survival versus placebo and is a potential new standard of care" in patients with fully resected intermediate- to high-risk ccRCC, said Dr. Tony Choueiri of Dana-Farber Cancer Institute in Boston in a presentation of the results at the American Society of Clinical Oncology (ASCO) virtual annual meeting. The KEYNOTE-564 trial enrolled 994 patients with histologically confirmed ccRCC with an intermediate or high risk for recurrence or no evidence of disease after surgery. They had not received prior systemic therapy and had an ECOG performance status of zero or one. Half were randomly allocated to pembrolizumab and half to placebo taken for one year. At 24 months' median follow-up, patients receiving pembrolizumab had a 32% reduction in the risk of disease recurrence or death, Dr. Choueiri reported. The 24-month estimated disease-free survival (DFS) rate was 77% with pembrolizumab compared to 68% with placebo. The data for overall survival, a key secondary endpoint, are immature. However, the preliminary data favor pembrolizumab, with estimated 24-month overall survival of 96.6% with pembrolizumab compared to 93.5% with placebo. At data cutoff, there were 18 deaths in the pembrolizumab group versus 33 in the placebo group. The safety of pembrolizumab was in line with expectations overall and without any new safety signals. No treatment-related deaths occurred in the pembrolizumab group. Offering perspective following the presentation, Dr. Julie Gralow, ASCO chief medical officer, said, "The KEYNOTE-564 study 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 renal-cell carcinoma, which is the most common type of kidney cancer." "Despite surgery, recurrence is common in clear-cell renal-cell carcinoma, and if it does recur, there are limited curative treatment options. The results of the KEYNOTE-564 trial support consideration of pembrolizumab as a potential new standard of care in the adjuvant setting to reduce disease recurrence in certain patients with kidney cancer," said Dr. Gralow. Dr. Kai Tsao, medical director of Ruttenberg Treatment Center at The Tisch Cancer Institute at Mount Sinai, in New York City, told Reuters Health by email, "Given the high rate of recurrence for patients with high-risk localized clear cell RCC after nephrectomy, an effective and safe perioperative treatment to reduce recurrence remains an urgent need." Dr. Tsao, who was not involved in the study, noted that adjuvant sunitinib has been approved in the United States after demonstrating a definitive disease-free survival (DFS) benefit versus placebo in the randomized phase-3 study S-TRAC trial, "but to date this treatment approach has been largely underutilized." "Given the definitive DFS benefit demonstrated in KEYNOTE-564, we expect pembrolizumab will become an additional standard of care option in the adjuvant setting, to delay disease recurrence for patients with fully resected clear-cell RCC," Dr. Tsao told Reuters Health. Funding for the study was provided by Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc. Several authors have disclosed financial relationships with the company. —Megan Brooks Source
