Journal Article Epublish
PubMed: 42882910 DOI: 10.3390/cancers18193216
CABOPRE: Evaluating Perioperative Cabozantinib's Efficacy and Biomarkers for Cytoreductive Nephrectomy in Advanced Renal Cell Carcinoma.
Cancers (Basel) 18(19)
Authors: Guillermo de Velasco, Teresa Alonso-Gordoa, Juan Francisco Rodríguez-Moreno, Ignacio Duran, Lucía Carril Ajuria, Pablo Álvarez Ballesteros, Enrique González-Billalabeitia, José I Domínguez, Ana García-Casas, Enrique Pérez-Navarro, Sara Sánchez-Redondo, Javier Molina-Cerrillo, Felix Guerrero-Ramos, Ray Manneh Kopp, Cecilia Marinas, Jesús M Paramio, Héctor Peinado, Daniel Castellano, Marta Dueñas
Affiliations
- Medical Oncology/Urology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.
- Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), 28041 Madrid, Spain.
- Medical Oncology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
- IRYCIS (Instituto Ramón y Cajal de Investigación Sanitaria), 28034 Madrid, Spain.
- Instituto de Investigación Sanitaria HM Hospitales, 28015 Madrid, Spain. Facultad de Medicina, Universidad San Pablo CEU, 28925 Madrid, Spain.
- Oncology Department, Hospital Universitario Marques de Valdecilla, IDIVAL, 39008 Cantabria, Spain.
- Medical Oncology Department, CHU Saint Pierre, 1000 Brussels, Belgium.
- Medical Oncology/Urology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain. Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), 28041 Madrid, Spain.
- Departamento de Ingeniería de la Información y las Comunicaciones, Universidad de Murcia, 30100 Murcia, Spain.
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain.
- Medical Oncology, Sociedad de Oncología y Hematología del Cesar, Valledupar 200001, Colombia.
- Molecular 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.
MeSH
Cells, Neoplasms, Nephrectomy, Carcinoma, Renal Cell, Biomarkers, Therapeutics