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)