Federica Sordelli, Giuseppe Basile, Eduard Roussel, Veda Kudva, Daniel Hughes, Elizabeth Nally, Ravi Barod, Abhishek Reekhaye, Mark Yao, Alzahrani Hani, Prasad Patki, Faiz Mumtaz, Soha El Sheikh, Omid Sedigh, Nicolò Maria Buffi, Ekaterini Boleti, Thomas Powles, Axel Bex, Antonio Rullan
The safety and oncological outcomes of adjuvant pembrolizumab in routine clinical practice within a UK tertiary renal cancer network were consistent with those reported in the KEYNOTE-564 trial. Treatment decisions should extend beyond trial-based eligibility and incorporate validated recurrence risk tools, comorbidities, and patient preferences through individualized counselling and shared decision-making.
BACKGROUND: Adjuvant pembrolizumab has become the standard of care for patients with clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence after surgery. However, evidence regarding its uptake, safety, and oncological outcomes in routine clinical practice remains limited.
OBJECTIVE: To assess the uptake, oncological outcomes, and safety of adjuvant pembrolizumab among patients eligible according to the KEYNOTE-564 criteria within a UK tertiary renal cancer network.
DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed patients with surgically treated ccRCC who were eligible for adjuvant pembrolizumab and whose cases were discussed at the multidisciplinary team (MDT) of a UK tertiary renal cancer network between November 2022 and April 2024.
INTERVENTION: Following individualized counselling and shared decision-making, patients received adjuvant pembrolizumab or underwent surveillance.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Study outcomes included discussion of treatment eligibility at the MDT, patients' and clinicians' joint decision regarding adjuvant pembrolizumab, the incidence and type of treatment-related adverse events (TRAEs), treatment discontinuation rate, and management strategies following disease recurrence. Oncological outcomes included disease-free survival (DFS) and overall survival (OS). Survival outcomes were estimated using the Kaplan-Meier method.
RESULTS AND LIMITATIONS: Of 154 patients eligible for adjuvant pembrolizumab, 129 were medically fit to receive treatment, of whom 50% declined therapy following counselling. Patients treated with pembrolizumab were younger than those undergoing surveillance (median age 61 vs 67 yr; p < 0.001), had higher tumour necrosis (45% vs 30%; p = 0.075), and had high-risk disease according to the Leibovich score (53% vs 42%; p = 0.2). At 24 mo, the estimated DFS and OS among patients treated with adjuvant pembrolizumab were 69% (95% confidence interval [CI] 55-87) and 95% (95% CI 89-100), respectively. Regarding safety, 92% of treated patients experienced any-grade TRAEs, 19% experienced grade ≥3 TRAEs, 33% required corticosteroids, and 23% discontinued treatment because of toxicity. The retrospective, nonrandomized design and relatively short follow-up represent the main study limitations.
CONCLUSIONS: The safety and oncological outcomes of adjuvant pembrolizumab in routine clinical practice within a UK tertiary renal cancer network were consistent with those reported in the KEYNOTE-564 trial. Treatment decisions should extend beyond trial-based eligibility and incorporate validated recurrence risk tools, comorbidities, and patient preferences through individualized counselling and shared decision-making.