1. Symposium 2: Sarcoma of the Year – Synovial Sarcoma Peter Reichardt HELIOS Klinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg

2. 1 Taxonomy of soft tissue sarcoma Taylor et al., Nat Rev Oncology 2011 HELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-BrandenburgP. Reichardt

3. 2 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

4. 3 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

5. 4 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

6. 5 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

7. 6 Synovial sarcoma - Ifosfamide P. ReichardtHELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg

8. 7 Synovial sarcoma – Combination chemotherapy P. ReichardtHELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg

9. 8 Synovial sarcoma – Combination chemotherapy P. ReichardtHELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg

10. 9 Synovial sarcoma - Gefitinib P. ReichardtHELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg

11. 10 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

12. 11 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

13. 12 Synovial sarcoma – adjuvant therapy P. ReichardtHELIOS 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

14. 13 P. ReichardtHELIOS KLinikum Berlin-Buch / Sarcoma Center Berlin-Brandenburg Le Cesne et al., ASCO 2008, #10525 Synovial sarcoma – adjuvant therapy (EORTC Meta-analysis)