New breakthroughs and future trends in renal cell carcinoma therapy: Highlights from the 2025 European Society for Medical Oncology Annual Congress

Table 1 Summary of key studies on renal cell carcinoma at the European Society for Medical Oncology 2025 Congress

Ref.	Study name	Study design	Main findings
Burgers et al[3], 2025	NESCIO	Phase II randomized controlled trial	The ipilimumab plus nivolumab group and the relatlimab plus nivolumab group both met the prespecified primary endpoint of pathologic response, demonstrating clear antitumor activity, with the short-course (6-week) therapy being well-tolerated
Haake et al[6], 2025	OPTIC RCC	Prospective phase II multicenter study	Targeted immunotherapy based on molecular subtypes achieved a higher ORR in the selected population compared to historical controls (nivolumab plus cabozantinib) (75% vs 55%)
Hahn et al[20], 2025	LenCabo	Multicenter phase II randomized controlled trial	Lenvatinib plus everolimus vs cabozantinib monotherapy: Superior median PFS (15.7 months vs 10.2 months), reducing disease progression risk by 49% (HR = 0.51); higher ORR (52.6% vs 38.6%); but higher incidence of grade ≥ 3 adverse events (67.5% vs 50.0%)
Huang et al[25], 2025	Dynamic ctDNA-MRD Monitoring	Cohort study	ctDNA levels decreased significantly after treatment; patients with persistently negative MRD had a lower risk of disease progression, and their median PFS was significantly longer than that of MRD-positive patients (not reached vs 14 months)
Huang et al[23], 2025	CLEAR-IT	Phase II study	Cadonilimab plus lenvatinib in patients progressing on prior immunotherapy: ORR was 29%, DCR was 96%, median PFS was 16.8 months, with a low incidence of grade ≥ 3 TRAEs (12.5%)
Kim et al[10], 2025	AI-based Immune Phenotype Analysis Model	Cohort study	Patients with an “inflammatory” phenotype had significantly better PFS, OS, and ORR with dual immunotherapy (nivolumab plus ipilimumab) than with sunitinib, while no significant difference in efficacy was observed between the two treatments in patients with a “non-inflammatory” phenotype
Larkin et al[2], 2025	RAMPART	Phase III randomized controlled trial	Durvalumab plus tremelimumab vs active surveillance significantly improved DFS in the overall population (2-year DFS rate: 81% vs 73%); the significant benefit was entirely driven by the high-risk recurrence population (HR = 0.52), with no clear benefit observed in the intermediate-risk group
Machaalani et al[9], 2025	Soluble MAdCAM-1 Translational Study	Cohort study	Higher baseline plasma soluble MAdCAM-1 (sMAdCAM-1) levels were independently associated with longer PFS and OS
Seront et al[24], 2025	RENALUT	Multicenter, open-label phase II trial	First exploration of 177Lu-PSMA-617 radioligand therapy in RCC resistant to both TKIs and ICIs; the study is ongoing, and results are pending
Simsek et al[8], 2025	COSMIC-313	Randomized controlled trial	Density of a specific CD8+ T-cell subset (CD8+ PD-1 + TIM-3-LAG-3 TILs) significantly correlated with efficacy: The high-density group had an ORR of 60.4% and median PFS was not reached; the low-density group had an ORR of 37.9% and median PFS was only 9.3 months
Ye et al[26], 2025	FRUSICA-2	Phase III randomized controlled trial	Compared to standard second-line monotherapy (axitinib or everolimus), the combination regimen significantly extended median PFS to 22.21 months (vs 6.90 months) and increased ORR to 60.5% (vs 24.3%), without increasing treatment-related death risk

NESCIO: Neoadjuvant Immuno-Oncology Trial in Localized Renal Cell Carcinoma; OPTIC RCC: OPtimal Treatment by Invoking biologic Clusters in Renal Cell Carcinoma; ORR: Overall response rate; PFS: Progression-free survival; HR: Hazard ratio; ctDNA-MRD: Circulating tumor DNA-minimal residual disease; CLEAR-IT: Clear Cell Renal Cell Carcinoma Immunotherapy Trial; DCR: Disease control rate; TRAEs: Treatment-related adverse events; OS: Overall survival; RAMPART: Durvalumab Plus Tremelimumab Versus Placebo in the Adjuvant Treatment of High-Risk Renal Cell Carcinoma; DFS: Disease-Free Survival; MAdCAM-1: Mucosal addressin cell adhesion molecule-1; RENALUT: Renal Cell Carcinoma PSMA-Targeted Therapy Trial; TKIs: Tyrosine kinase inhibitors; ICIs: Immune checkpoint inhibitors; COSMIC-313: Cabozantinib, Nivolumab, and Ipilimumab Versus Cabozantinib and Nivolumab in Advanced Renal Cell Carcinoma; FRUSICA-2: Fruquintinib Plus Sintilimab in Previously Treated Advanced Renal Cell Carcinoma.