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Prognostic risk models for OS in patients with metastatic clear cell renal cell carcinomarognostic risk models for OS in patients with metastatic clear cell renal cell carcinomarognostic risk models for OS in patients with metastatic clear cell renal cell carcinomarognostic risk models for OS in patients with metastatic clear cell renal cell carcinomarognostic risk models for OS in patients with metastatic clear cell renal cell carcinomarognostic risk models for OS in patients with metastatic clear cell renal cell carcinomarognostic risk models for OS in patients with metastatic clear cell renal cell carcinoma
CABOPRE: A phase II study of CABOZANTINIB prior cytoreductive nephrectomy
(CN) in metastatic renal cell carcinoma (mRCC)
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Guillermo de Velasco , Teresa Alonso , Juan Francisco Rodríguez-Moreno , Ignacio Duran , Alberto Carretero-González , M. Cruz Martín-Soberón , José
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Luis Gutiérrez Baños , Félix Guerrero , Marta Dueñas , Daniel Castellano 1
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1 University Hospital 12 de Octubre, Madrid; University Hospital Ramón y Cajal, Madrid; University Hospital HM Sanchinarro, Madrid; University Hospital Marqués de
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Valdecilla, Santander; Molecular Biology Unit at CIEMAT-Fundación de Investigación Hospital 12 de Octubre, Madrid
BACKGROUND RESULTS
Favourable response to systemic therapy has been suggested as a Table 1. Patients Characteristics Table 2. Summary of efficacy endpoints Table 3. Treatment-related adverse events
suitable approach to select ideal candidates for CN in mRCC.
Cabozantinib demonstrated a clinical benefit as first-line therapy in Median age -years 56.5 (49.0, 63.0) Objetive response rate at 12 weeks N=15 Adverse events All Grade
(N=18)
66.6%/33.3%
Male/Female
grades 3/4
mRCC patients with intermediate- or poor-risk International Metastatic WHO PS 0:/1: 33.6%/66.6% (95% CI) 26.7% Asthenia 12 (67) 1 (6)
Renal Cell Carcinoma Database Consortium criteria (IMDC) as well as IMDC intermediate/poor risk 77.7%/22.3% Best response rate n (%) Hypertension 10 (55) 0 (0)
second-line therapy . CABOPRE trial was designed as an open-arm ≥ 2 measurable metastatic sites 77.7% Partial response 26,7% Diarrhea 10 (55) 0 (0)
1-2
prospective multicentre phase II trial to assess the efficacy and safety Mean primary tumour size 96 mm Stable disease 66,7% Mucositis 7 (39) 0 (0)
of cabozantinib 60 mg/daily, given as perioperative treatment in Clear cell histology N=18 (100%) Progressive disease 6,7% Hyporexia 6 (33) 0 (0)
potential candidates to CN (EudraCT Number: 2018-001201-93) CN performed N = 11/16 (68.8%)*2 not evaluable Not evaluable 3 patients Hand-foot syndrome 4 (22) 0 (0)
Disease control rate 93,3% Dysphonia 3 (16) 0 (0)
Median progression-free survival 12,7 months Hypothyroidism 3 (16) 0 (0)
METHODS and STATISTICS Figure 1. Progression free survival Kaplan-Meier curve by RECIST
Figure 3. Hieralchical Cluster of miRNA expression in plasma from pre (A) and Post (B)
❖Eligible patients had clear cell mRCC and ECOG performance status treatment samples.
of 0 to 1 and were intermediate or poor risk per IMDC. The primary
endpoint was objective response rate (ORR) at 12 weeks (prior CN).
Progression-free survival (PFS), overall survival (OS), safety and miRNA expression in plasma
exploratory biomarkers analysis (sequential tumour biopsies and samples analysis using
peripheral blood) were secondary end points. Nanostring miRNA
expression panel V3. We
❖ Median PFS 12,7 months (5.1,-) found 61 differentially
❖ 12-months PFS 56% expressed miRNAs that
correctly classified samples
pervious and post treatment
with Cabozantinib. Figure
shows the clustering for 5
months assayed samples.
Figure 2.Overall survival Kaplan-Meier curve by RECIST
❖From Dec 2018 to Dec 2020, 18 patients were enrolled at 4 University Conflicts of Interest
Hospitals in Spain.
GDV (Consulting, advisory role or honoraria) with BMS; Ipsen, Pfizer, MSD; Merck, Roche, Astellas, Bayer, Eusa Pharma.
CONCLUSIONS References
❖ 12-months OS 70%
1. Choueiri TK, et al. Eur J Cancer. 1 de mayo de 2018;94:115-25.
❖ Cabozantinib as perioperative treatment is feasible and induce 2. Choueiri TK, et al. N Engl J Med. 5 de noviembre de 2015;373(19):1814-23.
rapid responses in intermediate/poor-risk mRCC patients enabling
selection for CN. Acknowledgments
❖ Dynamic biomarkers may be key for treatment assessment. months Study support provided by Ipsen. Sponsor: Oncosur
Additional studies are ongoing.
Guillermo_deVelasco@dfci.harvard.edu
ESMO 2021 676P @g_develasco gdvelasco.gdv@gmail.com
GenitoUrinary Symposyum 2017
toni_choueiri@dfci.harvard.edu