Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma.
BACKGROUND
Adult "translocation" renal cell carcinoma (RCC), bearing transcription factor E3 (TFE3) gene fusions at Xp11.2, is a recently recognized, unique entity for which prognosis and therapy remain poorly understood. In the current study, the authors investigated the effect of vascular endothelial growth factor (VEGF)-targeted therapy in this distinct subtype of RCC.


METHODS
A retrospective review was conducted to describe the clinical characteristics and outcome of adult patients with metastatic Xp11.2 RCC who had strong TFE3 nuclear immunostaining and received anti-VEGF therapy. Tumor response to anti-VEGF therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions.


RESULTS
Fifteen patients were identified, of whom 10, 3, and 2 received sunitinib, sorafenib, and monoclonal anti-VEGF antibodies, respectively. The median follow-up was 19.1 months, the median age of the patients was 41 years, and the female:male ratio was 4:1. Initial histologic description included clear cell (n = 8 patients), papillary (n = 1 patient), or mixed clear cell/papillary RCC (n = 6 patients). Five patients had received prior systemic therapy. Five patients had undergone fluorescent in situ hybridization analysis and all demonstrated a translocation involving chromosome Xp11.2. When treated with VEGF-targeted therapy, 3 patients achieved a partial response, 7 patients had stable disease, and 5 patients developed progressive disease. The median PFS and OS of the entire cohort were 7.1 months and 14.3 months, respectively.


CONCLUSIONS
Adult-onset, translocation-associated metastatic RCC is an aggressive disease that affects a younger population of patients with a female predominance. In the current study, VEGF-targeted agents appeared to demonstrate some efficacy.
Choueiri
Toni K
TK
Dana-Farber Cancer Institute, Boston, MA, USA. Toni_Choueiri@dfci.harvard.edu
Lim
Zita Dubauskas
ZD
Hirsch
Michelle S
MS
Tamboli
Pheroze
P
Jonasch
Eric
E
McDermott
David F
DF
Dal Cin
Paola
P
Corn
Paul
P
Vaishampayan
Ulka
U
Heng
Daniel Y C
DY
Tannir
Nizar M
NM
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D041321:Chromosomes, Human, X; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D014178:Translocation, Genetic; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D007211:Indoles; D011758:Pyrroles; C069203:TFE3 protein, human; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib