Real-World Data Showcase Efficacy of Adjuvant Pembrolizumab in ccRCC

Adjuvant pembrolizumab (Keytruda) displayed strong efficacy with high disease-free survival (DFS) and overall survival (OS) rates, in addition to a manageable safety profile with low rates of severe adverse effects (SAEs), according to data from the observational, real-world ARON-1 study (NCT05287464) presented at the 2025 ESMO Congress.1,2

Findings from the trial showed that at a median follow-up of 15.4 months, patients with ccRCC at intermediate-high or high risk of recurrence who received up to 17 cycles of adjuvant pembrolizumab (n = 311) achieved a 2-year OS rate of 95% and a 2-year DFS rate of 69%. Moreover, recurrence occurred in 20% of patients, mostly occurring in the bones (5%) and lungs (11%). However, in patients 65 years of age or younger (HR 2.14; P = 0.005), those with sarcomatoid dedifferentiation (HR 2.54; P = 0.007), and patients with N1 disease (HR 5.42; P = 0.004) experienced worsened DFS outcomes.

Regarding safety, SAEs led to treatment discontinuation in 19% of patients, with the most common AEs being hypertransaminasemia, colitis, and nephritis in 4%, 4%, and 3% of patients, respectively. Trial investigators noted that long-term safety data were limited since the study was retrospective in nature with short follow-up.

“This large real-world study confirms pembrolizumab’s effectiveness and manageable safety profile in the adjuvant setting for intermediate-high– and high-risk ccRCC. Further research is needed to refine [patient] selection strategies and evaluate long-term outcomes,” lead study author Veronica Mollica, MD, PhD, and colleagues wrote in a poster presentation of the data. Mollica is a medical oncologist at ICCRS Azienda Ospedaliero-Universitaria di Bologna in Italy.

What was the rationale and design of the trial?

Investigators of the trial wanted to expand upon the limited available real-world data on adjuvant pembrolizumab’s effectiveness in ccRCC. In November 2021, the FDA approved adjuvant pembrolizumab for patients with RCC who are at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.3 The approval was supported by data from the phase 3 KEYNOTE-564 trial (NCT03142334).

ARON-1 was an international, multicenter, retrospective study that took place across 40 hospitals in 12 countries and enrolled patients who were at least 18 years of age with cytological or histologically confirmed ccRCC at intermediate-high or high risk of recurrence.1

Patients received pembrolizumab in the adjuvant setting for up to 17 cycles, with the trial’s primary end points being DFS and OS. Safety was a secondary end point.

Baseline characteristics of the trial revealed that patients had a median age of 61 years (range, 25-85), and most patients were male (74%). Additionally, patients were located in North America (31%), Europe (51%), and the rest of the world (18%). Most patients underwent radical nephrectomy (95%), while significantly fewer received partial nephrectomy (5%). Similarly, many patients were in the M0 disease (89%) and N0 disease ( 95%); significantly fewer had tumors that were M1 with no evidence of disease (11%) and N1 disease (5%).

Primary tumor stages for patients were T1, T2, T3, and T4 at rates of 5%, 8%, 83%, and 4%, respectively. Moreover, tumor nuclear grades for patients were 1, 2, 3, and 4, at rates of 1%, 26%, 83%, and 27%, respectively. Sarcomatoid de-differentiation was less common in patients, reported at a rate of 17%.

What were the additional data from the trial?

OS univariable Cox regression analysis showed a hazard ratio (HR) of 1.02 (95% CI, 0.59-1.75; P = 0.950) for nephrectomy and 5.05 (95% CI, 1.13-22.68; P = 0.035) for sarcomatoid differentiation. DFS univariable Cox regression analysis demonstrated a HR of 1.73 (95% CI, 0.63-4.80; P = 0.290) for nephrectomy and 2.10 (95% CI, 1.21-3.65; P = 0.008) for sarcomatoid differentiation.

References

1. Mollica V, Massari F, Manneh Kopp R, et al. 2672eP real-world evidences on adjuvant pembrolizumab for renal cell carcinoma: results from the multicenter ARON-1 study. Annals of Oncology. 2025;36(S1427). doi:10.1016/j.annonc.2025.08.3283
2. International multicentric study ARON-1. ClinicalTrials.gov. Updated November 26, 2025. Accessed December 8, 2025. https://clinicaltrials.gov/study/NCT05287464
3. FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. News release. FDA; November 17, 2021. Accessed December 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma