458 Background: In patients at increased risk of recurrence following surgical resection of RCC, adjuvant pembrolizumab has been shown to lower the risk of recurrence and improve overall survival. This treatment is now the standard of care in the UK. In the KEYNOTE 564 trial 96.3% of patients who received pembrolizumab experienced at least one adverse event and 32.4% of patients experienced an adverse event of grade 3-5. 38.9% of trial patients discontinued treatment early; 21.3% due to adverse events and 10.5% due to disease recurrence. 7.4% of patients who were treated with pembrolizumab required treatment with high dose systemic steroids (≥40mg prednisolone per day). Aims: To assess how real-world data from UK centres aligns with the outcomes reported in the KEYNOTE-564 trial. Methods: A retrospective analysis was conducted of 293 patients who received adjuvant pembrolizumab following surgical resection of RCC across 11 UK centres between 2022 and 2025. Data was collected on treatment-related toxicities, discontinuation rates, steroid use, and disease recurrence. Results: Between 2022 and 2025, 293 patients received adjuvant pembrolizumab. The median follow-up period was 11 months (range: 16–855 days). A total of 28 patients (9.6%) experienced disease recurrence, of which 16 (57.1%) occurred during treatment. At the time of analysis, 74 patients (25.3%) were still undergoing treatment, 107 patients (36.5%) had completed the full course, and 107 patients (36.5%) discontinued treatment early. Of those who discontinued, 89 patients (30.4%) stopped due to toxicity and 16 patients (5.4%) due to recurrence. Among patients who did not complete treatment, the mean number of cycles received was 4 (range: 1–8). Toxicities were varied, with the most commonly reported all-grade events being endocrine (27.6%), skin (23.6%), and arthralgia (11.3%). Grade 3 toxicities were observed in 39 patients (13.3%), and Grade 4 toxicities in 4 patients (1.4%). The most frequent toxicity leading to treatment discontinuation was colitis. Steroid use for toxicity management was reported in 100 patients (34.1%), with 57 patients (19.5%) receiving high-dose steroids. Additionally, 9 patients (3.1%) required further immunosuppression, including mycophenolate mofetil (4), methotrexate (3), and infliximab (2). Hospitalisation due to toxicity occurred in 43 patients (14.7%). There were three treatment-related deaths, attributed to pneumonitis, Triple M syndrome, and complications from nephritis and colitis. Conclusions: Data from 11 UK treatment centres indicate that discontinuation rates of adjuvant pembrolizumab due to toxicity are comparable to those reported in the KEYNOTE-564 trial. However, a higher proportion of patients in the real-world setting received high-dose steroid treatment (19.5%) compared to the trial population (7.4%).
McCarthy et al. (2026) studied this question.