Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare, molecularly defined subgroup of non-clear cell RCC (nccRCC) lacking an approved standard treatment. We report the exploratory analysis of this entity within the SUNNIFORECAST trial.
SUNNIFORECAST evaluated ipilimumab/nivolumab versus standard of care (SOC) in previously untreated, advanced nccRCC. The primary endpoint was the 12-months overall survival (OS) rate. Secondary endpoints included median OS, progression free survival (PFS) and overall response rate (ORR). PD-L1 expression was assessed exploratorily.
Of 309 randomized patients, 30 had centrally confirmed FH-deficient RCC (ipilimumab/nivolumab, n=14; SOC, n= 16). The 12-months OS rate was 85.7% (95% confidence interval [CI] 53.9-96.2%) versus 73.3% (95% CI 43.6-89.1%), median OS was 35.7 months (95% CI 16.8 months-NE) versus 24.7 months (95% CI 10.6-37.7 months, hazard ratio [HR] 0.46 [0.17-1.20]), and ORR 42.9% versus 33.3%, favoring ipilimumab/nivolumab. Twenty-four patients were evaluable for PD-L1 expression; 21 had a combined positive score (CPS) ≥1. In this subgroup, the 12-months OS rate was 80.0% (95% CI 40.9-94.6%) versus 72.7% (95% CI 37.1-90.3%), median OS 38.3 months (95% CI 8.8 months-NE) versus 24.7 months (95% CI 8.8 months-NE, HR 0.43 [0.14-1.34]) and ORR 40.0% versus 36.4% for ipilimumab/nivolumab versus SOC, respectively.
Exploratory analyses suggest trends toward improved 12-months OS-rate, median OS and ORR with ipilimumab/nivolumab versus SOC in FH-deficient RCC. The majority of tumors demonstrated PD-L1-expression (e.g. CPS ≥ 1), warranting further investigation in prospective studies.
Cancer treatment and research communications. 2026 Jul 18 [Epub ahead of print]
Marit Ahrens, John Haanen, Laurence Albiges, Marine Gross Goupil, Ekaterini Boleti, Gwenaelle Gravis, Aude Fléchon, Marc Oliver Grimm, Jens Bedke, Philippe Barthélémy, Daniel Castellano, Begona Mellado, Philipp Ivanyi, Sylvie Rottey, Anne Flörcken, Cristina Suárez, Jose P Maroto, Viktor Grünwald, Sjoukje Oosting, Jindrich Kopecky, Stefanie Zschäbitz, Martin Boegemann, Tomas Buchler, Guenter Niegisch, Peter J Goebell, Tom Waddell, Florence Joly, Frank Priou, Margitta Retz, Stefan Siemer, Uwe Zimmermann, Dorothee Deckbar, Iris Burkholder, Christine Stöhr, Arndt Hartmann, Lothar Bergmann, Interdisciplinary Renal Cell Carcinoma Working Group of the DKG (IAGN)
Goethe University Frankfurt, University Hospital, Department of Hematology and Medical Oncology, Frankfurt, Germany. Electronic address: ., Goethe University Frankfurt, University Hospital, Department of Hematology and Medical Oncology, Frankfurt, Germany; Netherlands Cancer Institute, Amsterdam and Leiden University Medical Center, Leiden, Netherlands and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Institut Gustave Roussy, Paris, France., Hopital Saint André, Département d'Oncologie, Bordeaux, France., Royal Free London NHS Foundation Trust, London, UK., Department of Medical Oncology, Institut Paoli-Calmettes, Aix Marseille Univ, INSERM, CNRS, CRCM, Immunity and Cancer Team, Marseille, France., Centre Léon Bérard, Lyon, France., Department of Urology, Jena University Hospital, Friedrich-Schiller University and Comprehensive Cancer Center Germany (CCCG), Jena, Germany., Clinic for Urology, University Hospital, Tuebingen, Germany and Dept. of Urology & Transplantation Surgery, Eva Mayr-Stihl Cancer Center, Klinikum Stuttgart, Stuttgart, Germany., Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Clinic of Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., Clinic for Oncology, Hospital Clinic de Barcelona, Spain., Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Claudia von Schelling Comprehensive Cancer Center, Hannover, Germany., Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium., Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Hematology, Oncology, and Tumor Immunology, Berlin, Germany., Medical Oncology, Vall d'Hebron Institut of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., San Pau Hospital, (Hospital de la Santa Creu i Sant Pau), Barcelona, Spain., Clinic for Urology and Clinic for Medical Oncology, University Hospital, Essen, Germany., University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Faculty Hospital Hradec Kralove, Hradec Kralove, Czech Republic., University Hospital, NCT Heidelberg, Heidelberg, Germany., University Hospital Münster, Clinic for Urology, Münster, Germany., Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic., Department of Urology, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, and Centre for Integrated Oncology (CIO) Düsseldorf, CIO ABCD (Aachen-Bonn-Cologne-Düsseldorf), Düsseldorf, Germany., Erlangen University Hospital, Department of Urology and Pediatric Urology, Erlangen, Germany., The Christie NHS Foundation Trust, Manchester, UK., Centre Régional de Lutte contre le Cancer François Baclesse, Caen, France., Hospital Center Departmental De Vendée, La-Roche-sur-Yon, France., Technical University of Munich, School of Medicine and Health, Department of Urology, TUM University Hospital, Munich, Germany., Department of Urology, Saarland University, Homburg/Saar, Germany., University Medical Center Greifswald, Clinic for Urology, Greifswald, Germany., Goethe University Frankfurt, University Hospital, Department of Hematology and Medical Oncology, Frankfurt, Germany., Department of Health Sciences, Fulda University of Applied Sciences, Fulda, Germany., Institute of Pathology University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Institute of Pathology University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Comprehensive Cancer Center Erlangen EMN (CCC ER-ERM), Erlangen, Germany.