PMID- 20154303 OWN - NLM STAT- MEDLINE DCOM- 20101207 LR - 20211203 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 21 IP - 9 DP - 2010 Sep TI - Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network. PG - 1834-1838 LID - S0923-7534(19)40054-9 [pii] LID - 10.1093/annonc/mdq029 [doi] AB - BACKGROUND: Xp11 translocation renal cell carcinoma (RCC) is an RCC subtype affecting 15% of RCC patients <45 years. We analyzed the benefit of targeted therapy [vascular endothelial growth factor receptor (VEGFR)-targeted agents and/or mammalian target of rapamycin (mTOR) inhibitors] in these patients. PATIENTS AND METHODS: Patients with Xp11 translocation/TFE3 fusion gene metastatic RCC who had received targeted therapy were identified. Nuclear TFE3 positivity was confirmed by reviewing pathology slides. Responses according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Overall, 53 patients were identified; 23 had metastatic disease, and of these 21 had received targeted therapy (median age 34 years). Seven patients achieved an objective response. In first line, median PFS was 8.2 months [95% confidence interval (CI) 2.6-14.7 months] for sunitinib (n = 11) versus 2 months (95% CI 0.8-3.3 months) for cytokines (n = 9) (log-rank P = 0.003). Results for further treatment (second, third, or fourth line) were as follows: all three patients receiving sunitinib had a partial response (median PFS 11 months). Seven of eight patients receiving sorafenib had stable disease (median PFS 6 months). One patient receiving mTOR inhibitors had a partial response and six patients had stable disease. Median OS was 27 months with a 19 months median follow-up. CONCLUSION: In Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC. FAU - Malouf, G G AU - Malouf GG AD - Department of Medicine, Institut Gustave Roussy, Villejuif. FAU - Camparo, P AU - Camparo P AD - Department of Pathology, Hopital Foch, Suresnes. FAU - Oudard, S AU - Oudard S AD - Department of Medical Oncology, Hopital Europeen Georges Pompidou. FAU - Schleiermacher, G AU - Schleiermacher G AD - Department of Pediatric Oncology, Institut Curie, Paris. FAU - Theodore, C AU - Theodore C AD - Department of Medical Oncology, Hopital Foch, Suresnes, France. FAU - Rustine, A AU - Rustine A AD - New York Medical College and Department of Medicine, Our Lady of Mercy Hospital Cancer Center, Bronx, NY, USA. FAU - Dutcher, J AU - Dutcher J AD - New York Medical College and Department of Medicine, Our Lady of Mercy Hospital Cancer Center, Bronx, NY, USA. FAU - Billemont, B AU - Billemont B AD - Department of Medical Oncology, Hopital Cochin. FAU - Rixe, O AU - Rixe O AD - Department of Medical Oncology, Hopital Pitie-Salpetriere, Paris. FAU - Bompas, E AU - Bompas E AD - Department of Medical Oncology, Centre Rene Gauducheau, Nantes. FAU - Guillot, A AU - Guillot A AD - Department of Medical Oncology, Institut de Cancerologie de la Loire, Saint Priest en Jarez. FAU - Boccon-Gibod, L AU - Boccon-Gibod L AD - Pathology Department, Hopital d'Enfants Armand Trousseau. FAU - Couturier, J AU - Couturier J AD - Department of Genetics, Institut Curie. FAU - Molinie, V AU - Molinie V AD - Department of Pathology, Hopital Saint Joseph, Paris, France. FAU - Escudier, B AU - Escudier B AD - Department of Medicine, Institut Gustave Roussy, Villejuif. Electronic address: escudier@igr.fr. LA - eng PT - Journal Article DEP - 20100212 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Antineoplastic Agents) RN - 0 (Antiviral Agents) RN - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) RN - 0 (Benzenesulfonates) RN - 0 (Immunosuppressive Agents) RN - 0 (Indoles) RN - 0 (Interferon-alpha) RN - 0 (Phenylurea Compounds) RN - 0 (Pyridines) RN - 0 (Pyrroles) RN - 0 (TFE3 protein, human) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 25X51I8RD4 (Niacinamide) RN - 9HW64Q8G6G (Everolimus) RN - 9ZOQ3TZI87 (Sorafenib) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - V99T50803M (Sunitinib) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adolescent MH - Adult MH - Antineoplastic Agents/therapeutic use MH - Antiviral Agents/therapeutic use MH - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics MH - Benzenesulfonates/therapeutic use MH - Carcinoma, Renal Cell/drug therapy/*genetics/secondary MH - Child MH - Child, Preschool MH - Chromosomes, Human, Pair 11/*genetics MH - Chromosomes, Human, X/*genetics MH - Everolimus MH - Female MH - *Gene Fusion MH - Humans MH - Immunosuppressive Agents/therapeutic use MH - Indoles/therapeutic use MH - Interferon-alpha/therapeutic use MH - Kidney Neoplasms/drug therapy/*genetics/pathology MH - Male MH - Middle Aged MH - Niacinamide/analogs & derivatives MH - Phenylurea Compounds MH - Pyridines/therapeutic use MH - Pyrroles/therapeutic use MH - Research Report MH - Retrospective Studies MH - Sirolimus/analogs & derivatives/therapeutic use MH - Sorafenib MH - Sunitinib MH - Survival Rate MH - TOR Serine-Threonine Kinases/antagonists & inhibitors MH - Translocation, Genetic/*genetics MH - Treatment Outcome MH - Vascular Endothelial Growth Factor A/antagonists & inhibitors MH - Young Adult EDAT- 2010/02/16 06:00 MHDA- 2010/12/14 06:00 CRDT- 2010/02/16 06:00 PHST- 2010/02/16 06:00 [entrez] PHST- 2010/02/16 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] AID - S0923-7534(19)40054-9 [pii] AID - 10.1093/annonc/mdq029 [doi] PST - ppublish SO - Ann Oncol. 2010 Sep;21(9):1834-1838. doi: 10.1093/annonc/mdq029. Epub 2010 Feb 12.