The FDA approved pembrolizumab (Keytruda) for the adjuvant treatment of renal cell carcinoma (RCC) for patients who have an intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions, the agency announced.

Approval was based on results from the KEYNOTE-564 trial, which demonstrated that adjuvant pembrolizumab following nephrectomy significantly improved disease-free survival (DFS), with 22% of patients in the immunotherapy arm experiencing events of recurrence or death versus 30% in the placebo arm (HR 0.68, 95% CI 0.53-0.87, P=0.001).

“Despite decades of research, limited adjuvant treatment options have been available for earlier-stage renal cell carcinoma patients who are often at risk for recurrence. In KEYNOTE-564, pembrolizumab reduced the risk of disease recurrence or death by 32%, providing a promising new treatment option for certain patients at intermediate-high or high risk of recurrence,” said Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute in Boston, in a news release from Merck, the drug’s manufacturer.

“With this FDA approval, pembrolizumab may address a critical unmet treatment need and has the potential to become a new standard of care in the adjuvant setting for appropriately selected patients,” added Choueiri, who reported results from study at the 2021 virtual American Society of Clinical Oncology (ASCO) annual meeting.

KEYNOTE-564 was a multicenter, randomized, double-blind, placebo-controlled trial of 994 patients with intermediate-high or high risk of recurrence of RCC, or stage M1 with no evidence of disease. Patients were randomized 1:1 to pembrolizumab (200 mg intravenously every 3 weeks) or placebo for up to 1 year until disease recurrence or unacceptable toxicity.

At the ASCO meeting, Choueiri reported 1- and 2-year DFS rates of 85.7% and 77.3% with pembrolizumab, compared with 76.2% and 68.1% with placebo, respectively. The overall survival (OS) rate reached 96.6% at 2 years in the pembrolizumab arm versus 93.5% in the placebo arm (HR 0.54, 95% CI 0.30-0.96), although the difference missed prespecified criteria for statistical significance. OS data were not mature at the time of the analysis, he said.

At least one adverse event (AE) of any grade occurred in nearly all patients — 96.3% in the pembrolizumab arm and 91.1% in the placebo arm. Grade ≥3 AEs of any cause occurred in 32.4% and 17.7%, respectively.

The most common adverse reactions (≥20%) occurring in patients on the trial were musculoskeletal pain, fatigue, rash, diarrhea, pruritus, and hypothyroidism.