Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network.
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.


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.


CONCLUSIONS
In Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC.
Department of Medicine, Institut Gustave Roussy, Villejuif.
G G
GG
Malouf
Department of Pathology, Hôpital Foch, Suresnes.
P
P
Camparo
Department of Medical Oncology, Hôpital Européen Georges Pompidou.
S
S
Oudard
Department of Pediatric Oncology, Institut Curie, Paris.
G
G
Schleiermacher
Department of Medical Oncology, Hôpital Foch, Suresnes, France.
C
C
Theodore
New York Medical College and Department of Medicine, Our Lady of Mercy Hospital Cancer Center, Bronx, NY, USA.
A
A
Rustine
New York Medical College and Department of Medicine, Our Lady of Mercy Hospital Cancer Center, Bronx, NY, USA.
J
J
Dutcher
Department of Medical Oncology, Hôpital Cochin.
B
B
Billemont
Department of Medical Oncology, Hôpital Pitié-Salpétrière, Paris.
O
O
Rixe
Department of Medical Oncology, Centre René Gauducheau, Nantes.
E
E
Bompas
Department of Medical Oncology, Institut de Cancérologie de la Loire, Saint Priest en Jarez.
A
A
Guillot
Pathology Department, Hopital d'Enfants Armand Trousseau.
L
L
Boccon-Gibod
Department of Genetics, Institut Curie.
J
J
Couturier
Department of Pathology, Hôpital Saint Joseph, Paris, France.
V
V
Molinié
Department of Medicine, Institut Gustave Roussy, Villejuif. Electronic address: escudier@igr.fr.
B
B
Escudier
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D001557:Benzenesulfonates / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D000068338:Everolimus; D005260:Female; D050939:Gene Fusion; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D058028:Research Report; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014178:Translocation, Genetic / Q000235:genetics*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D055815:Young Adult
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001557:Benzenesulfonates; D007166:Immunosuppressive Agents; D007211:Indoles; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; C069203:TFE3 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068338:Everolimus; D000077157:Sorafenib; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib; D020123:Sirolimus