Outcome of chemotherapy in synovialsarcoma (sys) patients (pts): review of 15clinical trials from EORTCc involvingadvanced sys compared to other Soft TissueSarcomas (STS)
Winette T. van der Graaf, Elisa Rizzo , AlessandroGronchi, Ian Judson, Hans Gelderblom, SandrineMarreaud and Saskia Litiere,
on behalf of the EORTC Soft Tissue and BoneSarcoma Group
Disclosures
•Research grants from Novartis, Pfizer, GSK
2
Background
3
•Synovial sarcoma (SyS) represents about 8% of all soft tissuesarcomas
•SyS is a relatively more common among teenagers and youngadults
•The impression is that it is a more chemosensitive STS
• As outcome in metastatic session has not been reported tohave become significantly better during the last decades, weneed new synovial sarcoma specific studies.
•Therefore we need solid outcome data as basis for thestatistical design of new studies.
Aim
4
To evaluate :
•The clinical presentation of SyS pts
•The outcome of pts with advanced or metastatic SyS treatedwith first line chemotherapy.
Patients and Methods
5
•Data were used from the EORTC-STBSG database containing informationon
chemo-naïve advanced and metastatic STS pts who participated infifteen chemotherapy trials between 1976 and 2012.
•Pts with SyS were compared with other STS patients.
We evaluated overall survival (OS), progression free survival (PFS) andresponse rate (RR).
The chemotherapy in SyS pts was aggregated in 5 categories:
A: anthracyclines alone (121 pts) ,
B: ifosfamide alone (42),
C: doxorubicin and ifosfamide (112 pts),
D: CYVADIC (42 pts)
E: Other: Brostallicin, Trabectedin (8pts).
Selection of Synovial sarcoma patients
6
From the 15 EORTCpooled sarcomatrials,
313 patients withSyS sarcoma
were identified foranalysis.
3676 patients in theEORTC sarcoma database
192 received priortreatment
313 SySpatients
3171 Othersubtypes
3484 received noprior treatment
Characteristics of SyS pts compared to others STS pts
7
8
a Kruskal -Wallis test; b Chi-square test
RESULTS
9
OS
PFS
RR
OS Synovial vs. other sub-types
10
(months)
0
6
12
18
24
30
36
42
0
10
20
30
40
50
60
70
80
90
100
O
N
Number of patients at risk :
Tumor site
254
313
266
184
113
70
38
21
15
2546
3171
2242
1356
844
567
397
278
197
Synovial sarcoma
Other types
Overall Score test: p=0.009
Tumor site
Median (95% CI)(Months)
% at 1 Year(95% CI)
Synovial sarcoma
15.0 (13.9, 16.4)
63.7 (57.9, 68.8)
Other types
11.6 (11.1, 12.0)
48.0 (46.2, 49.8)
PFS Synovial vs. other sub-types
11
(months)
0
6
12
18
24
30
36
42
48
0
10
20
30
40
50
60
70
80
90
100
O
N
Number of patients at risk :
Tumor site
302
313
165
56
30
15
10
8
5
2979
3171
1169
513
290
191
143
111
92
Synovial sarcoma
Other types
Overall Score test: p=0.004
Tumor site
Median (95% CI)(Months)
% at 1 Year(95% CI)
Synovial sarcoma
6.3 (5.8, 6.9)
18.2 (14.2, 22.6)
Other types
3.6 (3.4, 3.9)
16.7 (15.4, 18.0)
OS univariate analysis
12
OS by Performance status
13
(months)
0
6
12
18
24
30
36
42
48
0
10
20
30
40
50
60
70
80
90
100
O
N
Number of patients at risk :
Performance status
121
157
145
110
68
45
27
15
13
114
136
110
70
43
25
11
6
2
15
16
7
2
0
0
0
0
0
PS 0
PS 1
PS 2+
Overall Score test: p<0.0001(df=2)
Performance status
Median (95% CI)(Months)
% at 1 Year(95% CI)
PS 0
17.7 (15.5, 19.7)
75.9 (68.2, 82.0)
PS 1
13.3 (10.8, 15.6)
55.6 (46.6, 63.6)
PS >=2
6.1 (3.1, 8.3)
14.3 (2.4, 36.3)
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OS multivariate analysis
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Factor
Hazard Ratio
95% Lower CL forHazard Ratio
95% Upper CL forHazard Ratio
P
Performancestatus
PS 1 vs. PS 0
1.63
1.24
2.13
<0.001
<0.001
PS 2+ vs. PS 0
5.80
3.06
11.01
Metastatic siteinvolved
Yes vs. No
1.53
1.15
2.04
0.004
Primary siteinvolved
Yes vs. No
3.13
1.71
5.73
<0.001
Better survival for Synovial patients:
•with WHO PS 0 vs. PS 1 & 2
•with metastatic site not involved
•the role of primary site involved is less clear as it is correlated withmetastatic site involved and it is not statistical significant in theunivariate analysis
No significant effect of chemotherapy regimen in first line treatmentobserved for OS
PFS univariate analysis
16
PFS by Performance status
17
(months)
0
6
12
18
24
30
36
0
10
20
30
40
50
60
70
80
90
100
O
N
Number of patients at risk :
Performance status
153
157
97
38
18
9
6
129
136
63
17
11
6
4
16
16
3
0
0
0
0
PS 0
PS 1
PS 2+
Overall Score test: p=0.000 (df=2)
Performance status
Median (95% CI)(year)
% at 1 Year(95% CI)
PS 0
0.6 (0.5, 0.7)
24.7 (18.2, 31.7)
PS 1
0.5 (0.3, 0.5)
13.7 (8.5, 20.2)
PS >=2
0.3 (0.2, 0.4)
0
18
19
PFS multivariate analysis
Factor
Hazard Ratio
95% Lower CL forHazard Ratio
95% Upper CL forHazard Ratio
P
Performancestatus
PS 1 vs. PS 0
1.41
1.10
1.80
0.007
0.004
PS 2+ vs. PS 0
2.42
1.33
4.40
Metastatic siteinvolved
Yes vs No
3.20
1.87
5.47
<.001
Better PFS for Synovial patients:
•with WHO PS 0 vs. PS 1 & 2
•with metastatic site not involved
Treatment was borderline not-significant (p=0.051) whenadjusting for the different potential prognostic factors for OS
Response to chemotherapy
20
RR to chemotherapy overall:28%; no change 46%
Conclusions
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•Prognostic impact of performance status and metastatic siteinvolved on OS an PFS
A better outcome for patients with PS 0 compared to PS ≥ 1 and withmetastatic site not involved
Variable primary site involved seems to be significant for OS but thisvariable is correlated with metastatic site involved
•There was no significant effect of treatment regimenobserved neither for PFS nor OS
•28% responders to chemotherapy among the SyS pts.
What next?
Given the fact that the prognosis of locallyadvanced and metastatatic SyS pts is still poor,we should consider cooperative groups for newclinical studies in this not so rare STS
WORK IN PROGRESS!!
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Acknowledgements
•Patients who participated in these studies
•All investigators of EORTC STBSG
•EORTC Headquarters
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Patients and Methods
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•Categorical variables were summarized by frequencies andpercentages,
•continuous variables were summarized by median, range,interquartile range (IQR).
•Comparisons between factors was done using chi-square or Kruskal-Wallis tests.
•Survival was estimated by Kaplan Meier method
•Univariate and multivariate analyses (using backward selection toreduce the multivariate model) were done using
Cox regression for PFS and OS
Logistic regression for RR