G G Malouf1, P Camparo2, S Oudard3, G Schleiermacher4, C Theodore5, A Rustine6, J Dutcher6, B Billemont7, O Rixe8, E Bompas9, A Guillot10, L Boccon-Gibod11, J Couturier12, V Molinié13, B Escudier14. 1. Department of Medicine, Institut Gustave Roussy, Villejuif. 2. Department of Pathology, Hôpital Foch, Suresnes. 3. Department of Medical Oncology, Hôpital Européen Georges Pompidou. 4. Department of Pediatric Oncology, Institut Curie, Paris. 5. Department of Medical Oncology, Hôpital Foch, Suresnes, France. 6. New York Medical College and Department of Medicine, Our Lady of Mercy Hospital Cancer Center, Bronx, NY, USA. 7. Department of Medical Oncology, Hôpital Cochin. 8. Department of Medical Oncology, Hôpital Pitié-Salpétrière, Paris. 9. Department of Medical Oncology, Centre René Gauducheau, Nantes. 10. Department of Medical Oncology, Institut de Cancérologie de la Loire, Saint Priest en Jarez. 11. Pathology Department, Hopital d'Enfants Armand Trousseau. 12. Department of Genetics, Institut Curie. 13. Department of Pathology, Hôpital Saint Joseph, Paris, France. 14. Department of Medicine, Institut Gustave Roussy, Villejuif. Electronic address: escudier@igr.fr.
Abstract
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.
BACKGROUND: Xp11 translocation renal cell carcinoma (RCC) is an RCC subtype affecting 15% of RCCpatients <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.
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