Symposium 2: Sarcoma of the Year – Synovial Sarcoma
Peter Reichardt
HELIOS Klinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg
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Taxonomy of soft tissue sarcoma
Taylor et al., Nat Rev Oncology 2011
HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-BrandenburgP. Reichardt
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Synovial sarcoma
• Synovial sarcoma accounts for approximately 8% of all soft tissue sarcomas.
• Higher incidence in adolescents and young adults (>50% between 10 and 40 years).
HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-BrandenburgP. Reichardt
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Distribution of histological subtypes
• Distribution of histological types: % of all sarcomas diagnosed in 3 European regions (Aquitaine and Rhône-Alpes in France, Veneto in Italy; 2005-2008):
Mastrangelo G, et al. Cancer. 2012 Apr 19. doi: 10.1002/cncr.27555.
HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-BrandenburgP. Reichardt
5P. Reichardt HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg
Individual sarcoma histologies as proportion of all soft tissue sarcoma (STS) by age according to Surveillance, Epidemiology and EndResults (SEER) data,1975-1999
Parham et al. ASCO 2011
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Synovial sarcoma
• Synovial sarcoma accounts for approximately 8% of all soft tissue sarcomas.
• Higher incidence in adolescents and young adults (>50% between 10 and 40 years).
• Typically affects the extremities (70%), case reports in multiple primary sites.
• Displays a variable degree of epithelial differentiation.
• Specific chromosomal translocation t(X;18)(p11;q11) that leads to formation of a SS18-SSX fusion gene.
HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-BrandenburgP. Reichardt
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Synovial sarcoma - Ifosfamide
P. Reichardt HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg
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Synovial sarcoma – Combination chemotherapy
P. Reichardt HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg
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Synovial sarcoma – Combination chemotherapy
P. Reichardt HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg
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Synovial sarcoma - Gefitinib
P. Reichardt HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg
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Synovial sarcoma: Options after doxo/ifo• Trabectedin: Retrospective pooled analysis including 45 SS patients:
• In other retrospective analysis of 61 SS patients, trabectedin showed an activity similar to that in leiomyosarcoma and liposarcoma, with a significant percentage of patients experiencing prolonged disease control (25% of cases therapy was continued for ≥5 m; Clinical benefit rate: 50%).
• Median PFS was 3.0 months and 6-month PFS rate of 22%.
• Median OS was 13.9 months, with 2 years survival rate of 28%.
Median OS Synovial: 13,9 months
Le Cesne A, et al. Eur J Cancer. 2012;48(16):3036-44; Sanfilippo R, et al. J Clin Oncol. 2010;28(Suppl15):712
HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-BrandenburgP. Reichardt
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• In the pazopanib registration study, 38 synovial sarcoma patients were included:
Synovial sarcoma: Options after doxo/ifo
Deeks E, et al. Drugs. 2012;72(16):2129-40; FDA Review NDA 022465/S-010 Votrient ® (pazopanib)
• Pazopanib significantly prolonged progression-free survival over placebo in this population (4.1 vs 1,0 months; HR=0.39).
• However, there was a lower survival with pazopanib vs placebo (8.7 vs 21.6 months) for this subtype.
HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-BrandenburgP. Reichardt
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Synovial sarcoma – adjuvant therapy
P. Reichardt HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg
• SS seems to be a subtype which benefits from adjuvant chemotherapy:
- In a retrospective analysis of 271 SS patients, among patients with macroscopically resected disease, those who received adjuvant chemotherapy had more favorable outcomes than those who did not receive chemotherapy (5-year MFS 60 vs. 48%).
Ferrari A, et al. Cancer. 2004;101(3):627-34
14P. Reichardt HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg
Le Cesne et al., ASCO 2008, #10525
Synovial sarcoma – adjuvant therapy (EORTC Meta-analysis)