Fumarate hydratase-deficient renal cell carcinoma – results of the exploratory analysis in the SUNNIFORECAST trial comparing Ipilimumab plus Nivolumab vs standard of care as first line treatment

Ahrens M, Haanen J, Albiges L, Goupil MG, Boleti E, Gravis G, Fléchon A, Grimm MO, Bedke J, Barthélémy P, Castellano D, Mellado B, Ivanyi P, Rottey S, Flörcken A, Suárez C, Maroto JP, Grünwald V, Oosting S, Kopecky J, Zschäbitz S, Boegemann M, Buchler T, Niegisch G, Goebell P, Waddell T, Joly F, Priou F, Retz M, Siemer S, Zimmermann U, Deckbar D, Burkholder I, Stöhr C, Hartmann A, Bergmann L (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 48

Article Number: 101319

DOI: 10.1016/j.ctarc.2026.101319

Abstract

Background: 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. Methods: 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. Results: 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. Interpretation / Discussion: 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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Münster Germany (DE) Thomayer University Hospital / Fakultní Thomayerovy nemocnice (FTN) Czech Republic (CZ) Universitätsklinikum Düsseldorf Germany (DE) Centre Hospitalier Départemental Vendée France (FR) Technische Universität München (TUM) Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Hochschule Fulda Germany (DE) Center François Baclesse / Centre Régional de Lutte contre le Cancer François Baclesse (CRLCC) France (FR) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald Germany (DE) Institut Gustave-Roussy France (FR) Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux France (FR) Royal Free London NHS Foundation Trust / Royal Free Hampstead NHS Trust United Kingdom (GB) CRCM Centre de Recherche en Cancérologie de Marseille France (FR) Centre Léon-Bérard (UNICANCER) France (FR) Universitätsklinikum Jena Germany (DE) Universitätsklinikum Tübingen Germany (DE) University Hospital Ghent Belgium (BE) Berliner Institut für Gesundheitsforschung in der Charité / Berlin Institute of Health at Charité (BIH) Germany (DE) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron Spain (ES) Hospital de la Santa Creu i Sant Pau Spain (ES) Universitätsklinikum Essen Germany (DE) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) University Hospital Hradec Králové / Fakultní Nemocnice Hradec Králové Czech Republic (CZ) Christie NHS Foundation Trust United Kingdom (GB) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Hôpitaux universitaires de Strasbourg (HUS) / University Hospital Strasbourg France (FR) Hospital Universitario 12 de Octubre Spain (ES) Hospital Clínic de Barcelona Spain (ES)

How to cite

APA:

Ahrens, M., Haanen, J., Albiges, L., Goupil, M.G., Boleti, E., Gravis, G.,... Bergmann, L. (2026). Fumarate hydratase-deficient renal cell carcinoma – results of the exploratory analysis in the SUNNIFORECAST trial comparing Ipilimumab plus Nivolumab vs standard of care as first line treatment. Cancer Treatment and Research Communications, 48. https://doi.org/10.1016/j.ctarc.2026.101319

MLA:

Ahrens, Marit, et al. "Fumarate hydratase-deficient renal cell carcinoma – results of the exploratory analysis in the SUNNIFORECAST trial comparing Ipilimumab plus Nivolumab vs standard of care as first line treatment." Cancer Treatment and Research Communications 48 (2026).

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