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. 2010 Nov 15;116(22):5219-25.
doi: 10.1002/cncr.25512.

Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma

Toni K Choueiri  1 , Zita Dubauskas Lim, Michelle S Hirsch, Pheroze Tamboli, Eric Jonasch, David F McDermott, Paola Dal Cin, Paul Corn, Ulka Vaishampayan, Daniel Y C Heng, Nizar M Tannir
Affiliations

Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma

Toni K Choueiri et al. Cancer. .

Abstract

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.

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Figures

Figure 1
Figure 1. FISH (fluorescence in situ hybridization) analysis showing a translocation involving chromosome X
Figure 2a
Figure 2a. Progression Free Survival of 7.1 months for 15 patients with advanced Xp11 translocation renal cell carcinoma treated with VEGF-targeted therapy
Figure 2b
Figure 2b. Overall Survival of 14.3 months for 15 patients with advanced Xp11 translocation renal cell carcinoma treated with VEGF-targeted therapy
Figure 3
Figure 3. Histologic appearance of Xp11.2 translocation RCC: nested/alveolar pattern with voluminous, eosinophilic/oncocytic cells (hematoxylin- eosin, original magnification, ×400)
See this image and copyright information in PMC

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