Nivolumab was approved for the treatment of previously treated advanced renal cell carcinoma (aRCC) following the results of the pivotal CheckMate-025 trial, which demonstrated a significant overall survival (OS) benefit over everolimus. However, due to the restrictive inclusion criteria of clinical trials, real-world evidence (RWE) is essential to better understand the effectiveness of nivolumab in unselected patient populations encountered in daily clinical practice. While several European RWE studies have been published, data from Spain have been lacking. Our study aimed to address this gap by evaluating the real-world outcomes of nivolumab monotherapy in a multicenter Spanish cohort.
Patients and Methods
We conducted a multicenter, retrospective cohort study including 222 patients with previously treated aRCC from 13 Spanish centers who received at least one dose of nivolumab in routine clinical practice between December 2015 and October 2021. Patients received nivolumab as second-line or later therapy. Demographic, clinical, pathological, and laboratory data were extracted from electronic medical records. The primary endpoint was overall survival, while secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR). Survival was analyzed using Kaplan–Meier methods, and prognostic factors were evaluated using Cox and logistic regression models.
Results
After a median follow-up of 14.6 months, median OS was 18.1 months, and median PFS was 4.96 months. The disease control rate reached 52% and the overall response rate was 23%, including a complete response rate of 7%. Poor IMDC risk score and the presence of three or more metastatic sites were independently associated with worse outcomes, while prior nephrectomy emerged as an independent factor associated with longer overall survival. Importantly, our cohort included a higher proportion of patients with unfavorable baseline characteristics compared with pivotal trials, including patients with non-clear cell histology, central nervous system metastases, and corticosteroid exposure.
Discussion and Clinical Context
The survival and response outcomes observed in our Spanish real-world cohort are consistent with those reported in previous RWE studies and in the CheckMate-025 trial, confirming the clinical activity of nivolumab outside of controlled trial settings. Although median OS was slightly shorter than in the pivotal trial and some RWE series, this likely reflects the inclusion of a more clinically complex population in routine practice. Notably, the rate of complete responses observed in our cohort was higher than that previously reported in several real-world studies.
The identification of poor IMDC risk and high metastatic burden as independent adverse prognostic factors aligns with existing literature. Prior nephrectomy remained an important, favorable prognostic factor, supporting its potential role even in the immunotherapy era. The inclusion of patient subgroups typically underrepresented in clinical trials provides valuable insight into nivolumab's effectiveness across a broader population.
Conclusion
This is the first large Spanish real-world study evaluating nivolumab monotherapy in previously treated aRCC. Our results reinforce the effectiveness of nivolumab in daily clinical practice and support its continued role as a treatment option in selected patients, particularly in settings where combination immunotherapy cannot be administered.
Written by: Natalia Fernández-Díaz,1,2,3 María Mateos-González,1,2 Ana Pertejo-Fernández,4 Juan Diego Cacho-Lavín,5 María José Juan-Fita,6 Isabel Chirivella-González,7 Mikel Arruti-Ibarbia,8 Ovidio Fernández-Calvo,9 Natalia Fernández-Núñez,10 María José Méndez-Vidal,11 Martín Lázaro-Quintela,12 Aurea Molina-Díaz,13 Nieves Del Pozo-Alonso,14 Olatz Etxaniz-Ulazia,15 Silvia Margarita García-Acuña,16 Yoel Z Betancor,2,3,17 Ainara Azueta-Etxebarria,18,19 Ana Calatrava-Fons,20 Helena Lombardía-Rodríguez,2,3 Lorena Alarcón-Molero,21,22 Leire Etxegarai-Ganboa,23 Abraham Antón-Cameselle,2,3 José Antonio Bello-Giz,24 Carlos Manuel Neira-De Paz,25 Teresa Cabaleiro,26 Teresa González-Serrano,27 José Antonio Ortiz-Rey,28 Felipe Sacristán-Lista,29 Silvia García-Rubín,2 Elisa Ortega,30 Cristina Carrato-Moñino,31 Santiago Aguín-Losada,1,2 Luis León-Mateos,1,2,3,32 Jorge García-González,1,2,32 Álvaro Pinto-Marín,4 Ignacio Duran,5 Rafael López-López,1,2,3,32 Urbano Anido-Herranz,1,2 Juan Ruiz-Bañobre,1,2,32,33
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain.
- Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
- University of Santiago de Compostela (USC), Santiago de Compostela, Spain.
- Department of Medical Oncology, Hospital Universitario La Paz - IdiPAZ, Madrid, Spain.
- Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
- Department of Medical Oncology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain.
- Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain.
- Department of Medical Oncology, Hospital Galdakao-Usansolo, Bizkaia, Spain.
- Department of Medical Oncology, Complejo Hospitalario Universitario de Ourense, Ourense, Spain.
- Department of Medical Oncology, Hospital Universitario Lucus Augusti, Lugo, Spain.
- Department of Medical Oncology, Hospital Universitario Reina Sofía, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain.
- Department of Medical Oncology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain.
- Department of Medical Oncology, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain.
- Department of Medical Oncology, Hospital Universitario del Vinalopó, Elche, Alicante, Spain.
- Department of Medical Oncology, Catalan Institute of Oncology (ICO), Hospital Germans Trias I Pujol, Badalona, Barcelona, Spain.
- Department of Pathology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain.
- Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain.
- Department of Pathology, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
- Department of Pathology, Basurto University Hospital, Translational Prostate Cancer Research Lab, CIC bioGUNE-Basurto, Biocruces Bizkaia Health Research Institute, Bilbao, Spain.
- Department of Pathology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain.
- Department of Pathology, Hospital Clínico Universitario de Valencia, Valencia, Spain.
- Department of Pathology, General Hospital of Valdepeñas, Ciudad Real, Spain.
- Department of Pathology, Hospital Galdakao-Usansolo, Bizkaia, Spain.
- Department of Pathology, Complejo Hospitalario Universitario de Ourense, Ourense, Spain.
- Department of Pathology, Hospital Universitario Lucus Augusti, Lugo, Spain.
- Fundación Pública Galega Instituto de Investigación Sanitaria de Santiago de Compostela, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
- Department of Pathology, Hospital Universitario Reina Sofía, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain.
- Department of Pathology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain.
- Department of Pathology, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain.
- Department of Pathology, Hospital Universitario del Vinalopó, Elche, Alicante, Spain.
- Department of Pathology, Hospital Germans Trias I Pujol, Badalona, Barcelona, Spain.
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.
- University of Santiago de Compostela (USC), Santiago de Compostela, Spain