CABOPRE: Evaluating Perioperative Cabozantinib’s Efficacy and Biomarkers for Cytoreductive Nephrectomy in Advanced Renal Cell Carcinoma
12 affiliations
- 1Medical Oncology/Urology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain
- 2Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), 28041 Madrid, Spain
- 3Medical Oncology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
- 4IRYCIS (Instituto Ramón y Cajal de Investigación Sanitaria), 28034 Madrid, Spain
- 5Instituto de Investigación Sanitaria HM Hospitales, 28015 Madrid, Spain
- 6Facultad de Medicina, Universidad San Pablo CEU, 28925 Madrid, Spain
- 7Oncology Department, Hospital Universitario Marques de Valdecilla, IDIVAL, 39008 Cantabria, Spain
- 8Medical Oncology Department, CHU Saint Pierre, 1000 Brussels, Belgium
- 9Departamento de Ingeniería de la Información y las Comunicaciones, Universidad de Murcia, 30100 Murcia, Spain
- 10Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain
- 11Medical Oncology, Sociedad de Oncología y Hematología del Cesar, Valledupar 200001, Colombia
- 12Molecular Oncology Unit, CIEMAT (Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas), 28040 Madrid, Spain
Abstract
Background/Objectives: Despite advances in metastatic renal cell carcinoma (mRCC), long-term survival is poor and biomarkers are lacking. Optimal integration of cytoreductive nephrectomy (CN) in the current era remains controversial. CABOPRE, the first phase II trial assessing perioperative cabozantinib in mRCC patients eligible for CN, aimed to determine its effects in this setting, integrating tumor outcomes with molecular profiling. Methods: CABOPRE (NCT06377722) is a multicentre, single-arm, phase II study conducted in Spanish academic hospitals. Patients with resectable metastatic clear cell RCC (ccRCC) eligible for post-treatment CN received perioperative cabozantinib (60 mg/day for 12 weeks; n = 18). The primary endpoint was the objective response rate (ORR) at 12 weeks assessed by RECIST v1.1. Exploratory analyses included longitudinal plasma miRNA and spatial transcriptomic profiling to identify candidate biomarkers. The trial closed early because of slow accrual, after enrolling 18 of 50 planned patients and without completing the 26-patient first stage of the Simon two-stage design; the planned interim analysis was therefore never performed. Results: Because the two-stage design was not completed, the primary endpoint could not be formally evaluated against the prespecified decision rule. Among 15 evaluable patients, the objective response rate was 26.7% (95% CI, 7.8–55.1), with stable disease in 10 (66.7%) and progressive disease in 1 (6.7%). Cabozantinib demonstrated a manageable safety profile (Grade 1–2 adverse events). In exploratory biomarker analyses, miR-126-3p upregulation and VEGFA/CCND1 downregulation were associated with tumor shrinkage, and the adhesion molecules ITGAV and ICAM1 were upregulated in these patients. Because no direct vascular measurements were performed, these changes are described as treatment-associated and hypothesis-generating rather than as predictors of response or evidence of vascular normalization. Conclusions: The observed response rate was close to the 25% null rate, and the prespecified efficacy rule could not be applied. CABOPRE provides preliminary evidence that perioperative cabozantinib is active and represents a viable backbone for neoadjuvant combination strategies in selected patients with potentially resectable mRCC. The identified molecular heterogeneity and stromal-immune signatures provide a biological rationale for the prospective evaluation of cabozantinib-IO combinations in this setting.
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BibTeX
@article{velasco2026cabopre,
title = {{CABOPRE: Evaluating Perioperative Cabozantinib’s Efficacy and Biomarkers for Cytoreductive Nephrectomy in Advanced Renal Cell Carcinoma}},
author = {Guillermo de Velasco and Teresa Alonso-Gordoa and Juan Francisco Rodríguez-Moreno and Ignacio Duran and Lucía Carril Ajuria and Pablo Álvarez Ballesteros and Enrique González-Billalabeitia and José I. Domínguez and Ana García-Casas and Enrique Pérez-Navarro and Sara Sánchez-Redondo and Javier Molina-Cerrillo and Felix Guerrero-Ramos and Ray Manneh Kopp and Cecilia Marinas and Jesús M. Paramio and Héctor Peinado and Daniel Castellano and Marta Dueñas},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18193216},
url = {https://europepmc.org/article/PMC/PMC13664424},
note = {CC BY},
}
RIS
TY - JOUR
TI - CABOPRE: Evaluating Perioperative Cabozantinib’s Efficacy and Biomarkers for Cytoreductive Nephrectomy in Advanced Renal Cell Carcinoma
AU - Guillermo de Velasco
AU - Teresa Alonso-Gordoa
AU - Juan Francisco Rodríguez-Moreno
AU - Ignacio Duran
AU - Lucía Carril Ajuria
AU - Pablo Álvarez Ballesteros
AU - Enrique González-Billalabeitia
AU - José I. Domínguez
AU - Ana García-Casas
AU - Enrique Pérez-Navarro
AU - Sara Sánchez-Redondo
AU - Javier Molina-Cerrillo
AU - Felix Guerrero-Ramos
AU - Ray Manneh Kopp
AU - Cecilia Marinas
AU - Jesús M. Paramio
AU - Héctor Peinado
AU - Daniel Castellano
AU - Marta Dueñas
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18193216
UR - https://europepmc.org/article/PMC/PMC13664424
AB - Background/Objectives: Despite advances in metastatic renal cell carcinoma (mRCC), long-term survival is poor and biomarkers are lacking. Optimal integration of cytoreductive nephrectomy (CN) in the current era remains controversial. CABOPRE, the first phase II trial assessing perioperative cabozantinib in mRCC patients eligible for CN, aimed to determine its effects in this setting, integrating tumor outcomes with molecular profiling. Methods: CABOPRE (NCT06377722) is a multicentre, single-arm, phase II study conducted in Spanish academic hospitals. Patients with resectable metastatic clear cell RCC (ccRCC) eligible for post-treatment CN received perioperative cabozantinib (60 mg/day for 12 weeks; n = 18). The primary endpoint was the objective response rate (ORR) at 12 weeks assessed by RECIST v1.1. Exploratory analyses included longitudinal plasma miRNA and spatial transcriptomic profiling to identify candidate biomarkers. The trial closed early because of slow accrual, after enrolling 18 of 50 planned patients and without completing the 26-patient first stage of the Simon two-stage design; the planned interim analysis was therefore never performed. Results: Because the two-stage design was not completed, the primary endpoint could not be formally evaluated against the prespecified decision rule. Among 15 evaluable patients, the objective response rate was 26.7% (95% CI, 7.8–55.1), with stable disease in 10 (66.7%) and progressive disease in 1 (6.7%). Cabozantinib demonstrated a manageable safety profile (Grade 1–2 adverse events). In exploratory biomarker analyses, miR-126-3p upregulation and VEGFA/CCND1 downregulation were associated with tumor shrinkage, and the adhesion molecules ITGAV and ICAM1 were upregulated in these patients. Because no direct vascular measurements were performed, these changes are described as treatment-associated and hypothesis-generating rather than as predictors of response or evidence of vascular normalization. Conclusions: The observed response rate was close to the 25% null rate, and the prespecified efficacy rule could not be applied. CABOPRE provides preliminary evidence that perioperative cabozantinib is active and represents a viable backbone for neoadjuvant combination strategies in selected patients with potentially resectable mRCC. The identified molecular heterogeneity and stromal-immune signatures provide a biological rationale for the prospective evaluation of cabozantinib-IO combinations in this setting.
SN - 2072-6694
ER -