Ilya Tsimafeyeu, Director of the Bureau for Cancer Research (BUCARE, USA/Russia), shared key insights on kidney cancer from ESMO 2025:
“Neoadjuvant Therapy
Dutch randomized phase 2 trial NESCIO: Neoadjuvant immunotherapy in patients with intermediate- and high-risk disease.
Treatment arms:
Two doses of either
- nivolumab, or
- nivolumab + ipilimumab, or
- nivolumab + relatlimab (anti-LAG3 antibody).
Primary endpoint: Pathologic response rate.
Results:
Nivolumab + ipilimumab and nivolumab + relatlimab achieved the predefined response rates, and the study will continue.
Data for nivolumab monotherapy were not presented.
Adjuvant Therapy
UK randomized phase 3 trial RAMPART: Adjuvant immunotherapy with durvalumab and tremelimumab in patients with intermediate- and high-risk disease.
Treatment arms (1 year):
- durvalumab, or
- durvalumab + tremelimumab, or
- active surveillance.
Primary endpoint: Disease-free survival (DFS).
Results:
The combination of durvalumab + tremelimumab reduced the risk of disease progression by 35%, which was statistically significant.
The absolute 3-year DFS difference was 8%.
Data for durvalumab monotherapy were not presented.
Reviewer’s comments:
- The durvalumab + tremelimumab combination was effective only in the high-risk cohort (no benefit in intermediate-risk).
- Patients with different RCC subtypes were included, but subtype-specific results were not presented.
- No data on subsequent treatment.
- No data yet on overall survival (OS).
First-Line Therapy for Metastatic RCC
Multi-cohort randomized trial KEYMAKER-U03: Pembrolizumab + lenvatinib in various combinations with additional agents in treatment-naïve patients with metastatic RCC.
Treatment arms:
- pembrolizumab + lenvatinib (control)
- pembrolizumab + lenvatinib + anti-LAG3
- pembrolizumab + lenvatinib + anti-CTLA-4
- pembrolizumab + lenvatinib + belzutifan
- pembrolizumab + anti-TIGIT + belzutifan
Primary endpoint: Objective response rate (ORR).
Results:
The pembrolizumab + lenvatinib control arm confirmed its known efficacy.
The best outcome was achieved with pembrolizumab + lenvatinib + belzutifan – with a similar ORR but a higher rate of complete and durable responses, a 55% reduction in risk of disease progression, and 18.5% more patients surviving beyond 2 years.
Other combinations produced inconclusive results.
Phase 2 trial OPTIC RCC: Efficacy of nivolumab + cabozantinib in patients with an angiogenic profile and nivolumab + ipilimumab in patients with an immune profile of metastatic RCC, both treatment-naïve.
Treatment arm presented:
- nivolumab + cabozantinib (first part of the trial).
Primary endpoint: Objective response rate (ORR).
Results: Nivolumab + cabozantinib showed a high response rate (76%) in patients with an angiogenic profile as defined by next-generation sequencing (NGS).
Differences were observed between the molecular profiles of primary kidney tumors and metastases, suggesting that future patient selection for nivo+cabo may require metastatic biopsy.
Phase 1b/2 trial: Evaluation of nivolumab + ipilimumab + ciforadenant (A2A adenosine receptor antagonist) in treatment-naïve patients with metastatic RCC.
Rationale: Blocking adenosine uptake enhances T-cell activity stimulated by immunotherapy.
Primary endpoint: Safety and evidence of clinical activity.
Results: The trial was negative – the combination did not improve efficacy.
Second and Later Lines of Therapy for Metastatic RCC
Randomized phase 2 trial LenCabo: Direct comparison of lenvatinib + everolimus vs cabozantinib in patients with metastatic RCC previously treated with 1–2 lines of immunotherapy or immuno-targeted therapy.
Treatment arms:
- lenvatinib + everolimus, or
- cabozantinib.
Primary endpoint: Progression-free survival (PFS).
Results: The combination of lenvatinib + everolimus outperformed cabozantinib across all endpoints: it reduced the risk of disease progression by 49% and increased the response rate by 14% compared to cabozantinib.
Chinese randomized phase 2/3 trial FRUSICO-2: Comparison of fruquintinib + sintilimab versus axitinib/everolimus in patients with metastatic RCC previously treated with targeted therapy.
Treatment arms: Immuno-targeted therapy vs targeted therapy.
Primary endpoint: Progression-free survival (PFS).
Results: The immuno-targeted therapy demonstrated a significant advantage over targeted therapy in later treatment lines. However, the reviewer raised multiple concerns regarding the study design and data quality.”
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