Case description
• 49-year-old man• 1st symptom/sign: Mild pain in right buttock
• 1st diagnosis:
Core-biopsy:
Monophasic Synovial Sarcoma
MRI:Heterogeneous mass
deeply located in right gluteus (maximus
and medius)
CT scan:
Metastases ruled out
April
2008
August
2008
Synovial Sarcoma G3T2bN0M0
• Neoadjuvant chemotherapy + radiotherapy:– Epirubicin 60 mg/m2/d d1-2+ Ifosfamide 3 g/m2/d d1-3/3 weeks GCSF x 3 cycles
along with radiotherapy (44 Gy)
• Marginal surgery with in block resection of the tumor and maximus gluteus and partial medium gluteus. Microscopical margin 0.3 mm
• Boost of 16 Gy
Case evolution: First treatment
In case of an early inoperable recurrence, what agents would you consider as options for the treatment of this synovial sarcoma patient?
a. Gemcitabine+DTIC or plus Docetaxelb. HD Ifosfamide c. Trabectedind. Pazopanib
• Anthracyclines + ifosfamide is strongly recommended for this entity, which seems to be the histotype which benefits most from ifosfamide.1
– High-dose ifosfamide as a single drug even after resistance to the combination, may be especially well suited for this entity.1
• Options after anthracyclines/ifosfamide:– Trabectedin: Several restrospective pooled analysis (N>100) showing an activity
similar to that in leiomyosarcoma and liposarcoma2-3 (Clinical benefit: 54%; median PFS: 3.0 months and median OS:13.9 months, with 2 years survival rate of 28%).2
– Pazopanib: Prolonged progression-free survival over placebo in this population (N=38; 4.1 vs 1,0 months; HR=0.39 p=0.005). However, there was a trend towards lower survival with pazopanib vs placebo (8.7 vs 21.6 months; HR=1.62 p=0.115) for this subtype.4-5
– Gemcitabine + docetaxel: In a retrospective review of 51 medical records, 43% achieved clinical benefit from the combination.6
Synovial sarcoma (SS): Treatment options
1. Eriksson M. Ann Oncol. 2010; 21(7):vii270–6; 2. Le Cesne A, et al. Eur J Cancer. 2012;48(16):3036-44; 3. Sanfilippo R, et al. CTOS 17th Annual Meeting. Prague, November 14-17, 2012. [Poster #107]; 4. Deeks E, et al. Drugs. 2012;72(16):2129-40; 5. Votrient ® Summary of
product characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001141/WC500094272.pdf ; 6. Sausan
Abouharb et al. J Clin Oncol. 2014; 32:5s (suppl; abstr 10564).
• Bilateral lung metastases 4 nodules ranging between 3 and 9 mm.
• Treatment: HD Ifosfamide 12 g/m2, 2 g/m2/d d1-6/ 21 d GCSF x 4 cycles.
• RECIST: SD
• Bilateral METASTASECTOMIES
Case evolution: First recurrenceJune
2009
Oct &
Nov
2009
• Appearance of 4 nodules in right lung
• Gemcitabine (1,800 mg/m2) + Dacarbazine (500 mg/m2) 15 d x 9 cycles
• Best Response: SD
Case evolution: Second recurrenceFeb
2010
• Bilateral lung metastases 4 nodules ranging between 3 and 9 mm.
Case evolution: New progressionJune
2010
Jun 2010
Jun 2010
Jun 2010
Jun 2010
Jun 2010
• Trabectedin 1.5 mg/m2 every 3 weeks X 17 cycles (up to 07/2011) Outcome: PR
Feb 2011
Feb 2011
Feb 2011
Feb 2011
Feb 2011
Four months after last cycle of trabectedin, there was a new progression, what therapeutic approach would you choose?
a. Gemcitabine +/- docetaxelb. Pazopanibc. Best supportive cared. Rechallenge with trabectedin
• Smaller time to progression with previous therapies:– HD Ifosfamide: 8 months– Gem/DTIC: 4 months– Trabectedin: 13 months
• Trabectedin safety profile allows long term treatment. In an analysis performed in more than a thousand of patients, no cumulative toxicities were apparent and it could be administered for up to 59 cycles.1
• Positive results of trabectedin rechallenge have been previously reported:2
– The rechallenge therapeutic strategy with trabectedin resulted in clinical benefit (CR+PR+SD) for about two thirds of patients after the first rechallenge and one third of patients after the second rechallenge.
What is the rationale supporting this decision?
1. Le Cesne A, et al. Invest New Drugs. 2012;30:1193-202; Saada E, et al. 2012 ASCO Annual Meeting. J Clin Oncol 30, 2012 (suppl; abstr 10062)
Trabectedin 1.5 mg/m2 x 10 cycles
Best Response: SD
Case evolution: Trabectedin rechallenge
Nov
2011
July 2012- Left paratracheal nodule.- Continue with trabectedin & RT 30 Gy targeting that nodule- Ongoing trabectedin- Best Response: PR
New Progression:
• Nodule in right middle lobe.• Continue with Trabectedin & RT 30 Gy targeting that nodule• Ongoing trabectedin• Best Response: PR
April 2013
Case evolution: Trabectedin rechallenge
June 2013
Case evolution: Last treatments
July
2013
Nov
2013
From November to February 2014: Epi+Ifos SD
Patient died on May 2014 after liver and
lung progression.
• Bilateral nodules• Pazopanib was started
• Up to Nov 2013• Best Response: SD
• Among the different treatments that this synovial patient received, trabectedin is the only agent able to bring partial responses and a long-term disease control.
• On the basis of this case report and findings from previous studies, trabectedin can be considered as an important therapeutic choice for the treatment of metastatic synovial sarcoma.
Case timeline and conclusions
1st recurrence HD Ifo 4cyMetasta-sectomy
Jun-Nov 2009
Feb 2010
Gem+DTIC 9cy SD
June 2010
Trabectedin 17cy PR
Nov 2011
Trabectedin 10cy SD
July 2012
Continue Trabectedin + RTP 30gy PR
April 2013
Continue Trabectedin + RTP 30gy PR
July 2013
Nov 2013
May 2014
Pazopanib SD
Epi + Ifo SD
Death
8 months 4 months 37 months 4 months 6 months