Fumarate hydratase-deficient (FHdef) renal cell carcinoma (RCC) is a rare entity associated with the hereditary leiomyomatosis and RCC syndrome with no standard therapy approved. The aim of this retrospective study was to evaluate the efficacy of different systemic treatments in this population.
We performed a multicentre retrospective analysis of Fhdef RCC patients to determine the response to systemic treatments. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and overall survival (OS). The two latter were estimated using the Kaplan-Meier method.
Twenty-four Fhdef RCC patients were identified, and 21 under systemic therapy were included in the analysis: ten received cabozantinib, 14 received sunitinib, nine received "other antiangiogenics" (sorafenib, pazopanib, and axitinib), three received erlotinib-bevacizumab (E-B), three received mTOR inhibitors, and 11 received immune checkpoint blockers (ICBs). ORR for treatments were 50% for cabozantinib, 43% for sunitinib, 63% for "other antiangiogenics," and 30% for E-B, whereas ORR was 0% for mTOR inhibitors and 18% for ICBs. The median TTF (mTTF) was significantly higher with antiangiogenics (11.6 months) than with mTOR inhibitors (4.4 months) or ICBs (2.7 months). In the first-line setting, antiangiogenics presented a higher ORR compared with nivolumab-ipilimumab (64% versus 25%) and a significantly superior mTTF (11.0 months vs 2.5 months; p = 0.0027). The median OS from the start of the first systemic treatment was 44.0 months (95% confidence interval: 13.0-95.0).
We report the first European retrospective study of Fhdef RCC patients treated with systemic therapy with a remarkably long median OS of 44.0 months. Our results suggest that antiangiogenics may be superior to ICB/mTOR inhibitors in this population.
European journal of cancer (Oxford, England : 1990). 2021 May 08 [Epub ahead of print]
Lucia Carril-Ajuria, Emeline Colomba, Luigi Cerbone, Carmen Romero-Ferreiro, Laurence Crouzet, Brigitte Laguerre, Constance Thibault, Cécile Vicier, Guillermo de Velasco, Aude Fléchon, Carolina Saldana, Patrick R Benusiglio, Brigitte Bressac-de Paillerets, Marine Guillaud-Bataille, Pauline Gaignard, Jean-Yves Scoazec, Stéphane Richard, Olivier Caron, Bernard Escudier, Laurence Albiges
Department of Medical Oncology, Gustave Roussy, Villejuif, France; Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain., Department of Medical Oncology, Gustave Roussy, Villejuif, France., CIBERESP, Instituto i+12, University Hospital 12 de Octubre, Madrid, Spain., Department of Medical Oncology, Centre Eugene Marquis, Rennes, France., Department of Medical Oncology, Hôpital Européen Georges-Pompidou, Paris, France., Department of Medical Oncology, Institute Paoli-Calmettes, Marseille, France., Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain., Department of Medical Oncology, Centre Léon-Bérard, Lyon, France., Department of Medical Oncology, Hôpital Henri Mondor Créteil AP-HP, France., UF d'Oncogénétique, Département de Génétique et Institut Universitaire de Cancérologie, GH Pitié-Salpêtrière, AP-HP Sorbonne Université F-75013 Paris, France., Service de Génétique, Molecular Genetic Department, GRCC, 94805 Villejuif, France., UF d'Oncogénétique, Département de Génétique et Institut Universitaire de Cancérologie, GH Pitié-Salpêtrière, AP-HP Sorbonne Université F-75013 Paris, France; Service de Génétique, Molecular Genetic Department, GRCC, 94805 Villejuif, France., Biochemistry Department, Hôpital Bicêtre, APHP Université Paris-Saclay, Le Kremlin Bicêtre F-94275, France., Department of Pathology, University Paris-Saclay, Gustave Roussy Cancer Center, Villejuif, France., Réseau National de Référence pour Cancers Rares de l'Adulte PREDIR labellisé par l'INCa, Hôpital Bicêtre, AP-HP, Le Kremlin Bicêtre, France; Génétique Oncologique EPHE, PSL Research University, Paris, France; UMR9019 CNRS Genome Integrity and Cancers, Institute Gustave Roussy, Villejuif, France., Laboratory Integrative Tumor Immunology and Genetic Oncology, Institute Gustave Roussy, Villejuif, France., Department of Medical Oncology, Gustave Roussy, Villejuif, France; Réseau National de Référence pour Cancers Rares de l'Adulte PREDIR labellisé par l'INCa, Hôpital Bicêtre, AP-HP, Le Kremlin Bicêtre, France., Department of Medical Oncology, Gustave Roussy, Villejuif, France; Réseau National de Référence pour Cancers Rares de l'Adulte PREDIR labellisé par l'INCa, Hôpital Bicêtre, AP-HP, Le Kremlin Bicêtre, France. Electronic address: .