Dr Haas on the Safety Profile of Adjuvant Pembrolizumab in Clear Cell RCC

“There have been no new safety signals observed. The predominant serious adverse effects that were [reported] among patients who received adjuvant pembrolizumab were hypertension and elevated transaminases.”

Naomi B. Haas, MD, the director of the Prostate and Kidney Cancer Program at the Abramson Cancer Center and a professor of medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania, discussed safety data from the 5-year follow-up of the phase 3 KEYNOTE-564 trial (NCT03142334) of adjuvant pembrolizumab (Keytruda) in patients with clear cell renal cell carcinoma.

Findings presented during the 2025 ASCO Annual Meeting revealed that there have been no new safety signals with pembrolizumab, Haas said. The most common grade 3 or higher adverse effects (AEs) among patients treated with pembrolizumab (n = 488) were hypertension (2.9%), increased alanine aminotransferase (2.3%), diarrhea (1.8%), and increased aspartate aminotransferase (1.6%), she added. All these AEs were reversible, Haas noted. Comparatively, these AEs occurred at grade 3 severity or higher in the placebo arm (n = 496) at respective rates of 2.6%, 0.2%, 0.2%, and 0.2%.

Any-grade AEs were reported at a rate of 96.3% in the pembrolizumab arm compared with 91.3% in the placebo arm. Patients in both arms experienced AEs leading to treatment discontinuation (21.1% vs 2.2%) and death (0.4% vs 0.2%). Any-cause serious AEs (SAEs; 20.7% vs 11.5%), any-grade treatment-related AEs (TRAEs; 79.1% vs 53.0%), grade 3 to 4 TRAEs (18.6% vs 1.2%), TRAEs leading to treatment discontinuation (18.2% vs 0.8%), treatment-related SAEs (11.9% vs 0.2%), immune-mediated AEs and infusion reactions (36.7% vs 7.3%), and grade 3 to 4 immune-mediated AEs and infusion reactions (9.6% vs 0.6%) were reported in both arms. No patients in either arm experienced TRAEs or immune-mediated AEs and infusion reactions that led to death.

Long-term AEs in the pembrolizumab arm included diabetes, Haas said. These AEs have been observed in clinical trials that enrolled patients with advanced disease as well as those in the adjuvant setting, she added. These AEs are not unique to pembrolizumab and have been reported with other immune checkpoint inhibitors, she concluded.