Transcript Document

Anatomic and Functional Imaging
Evaluation of a Clinical Trial of an
IGFR Antibody in Patients (PTS)
with Ewing Sarcoma (ES)
Vadim Koshkin; Vanessa Bolejack; Denise Reinke;
Rashmi Chugh; Lawrence Schwartz; Shreyaskumar
Patel; Lee Helman; Laurence Baker; Scott Schuetze
Disclosure: Marathon, Morphotek, Cytrx Inc
Response and Progression
in Solid Tumor Oncology
Response
Progression
Timing of Assessed early in treatment
Assessment: course
Assessed at intervals until
change of therapy
Not normally used to
Role in clinical
determine whether to change
Practice:
therapy
Commonly used to
determine when to change
therapy
Role in clinical Primarily used to calculate
Research: overall response rate
Primarily used to calculate
time to progression
endpoints
J Natl Cancer Inst. 2012 Oct 17;104(20):1534-41
The Evolution of Criteria for Determining Response and
Progression in Solid Tumor Oncology
Study and Year Published
Criteria
Response characteristics
Measurement method
Response criteria, % change
Equivalent % volume change*
Considers “clinical response”
Progression characteristics
Progression criteria, % change
Equivalent % volume change*
New lesions count as progression
Zubrod 1960
WHO 1980
SWOG 1992
RECIST 2009
Not described
Investigator consensus
NA
Yes
Bidimensional
50
65
Yes
Bidimensional
50
65
Yes
Unidimensional
30
66
No
Two consecutive increases
NA
Yes
25
40
Yes
50
84
Yes
20
73
Yes
* This calculation assumes a spherical tumor mass. NA = not applicable.
J Natl Cancer Inst. 2012 Oct 17;104(20):1534-41
SARC 011
• Multicenter trial of 115 patients with metastatic
Ewing’s sarcoma treated with IGF1R antibody
• Anatomic/functional imaging per protocol:
– CT/MR at baseline and at 6 week intervals…
– FDG PET (day 0, 9, 84)
• Anatomic imaging reported by the treating physician
• Anatomic imaging reviewed centrally- Larry Schwartz
• FDG PET imaging reviewed- Richard Wahl
Purpose
• To describe which patients do poorest
• To contrast sarcoma expert oncologists vs
radiology/nuclear medicine experts reading
• To contrast anatomic imaging vs FDG PET
• To explore new methodologies i.e. volumetrics
Secondary Analysis
Three types of progression:
1) Presence of new lesions
2) Increase in size of existing lesions
3) Both of the above
• We contrasted the type of progression with overall survival
• Compared local and central interpretation of progression
regarding overall survival
Local Interpretation of Week 6
Anatomic Imaging
104 patients
(available for analysis)
93 pts with Week 6
anatomic imaging
11 pts without Week 6
anatomic imaging
54 pts with Progressive Disease
39 pts with NonProgressive disease
(SD, CR, or PR)
Progression Based On:
1) Dimension criteria by WHO (N= 31)
2) Presence of new lesions (N=10)
3) Both dimension criteria and presence of new
lesions (N=13)
Survival Using Local Interpretation
N
P
P
P
N
100%
80%
o n P r o g r e s s iv e D is e a s e
D b y D im e n s io n
D b y N e w L e s io n
D b y N e w L e s io n + D im e n s io n
o W eek 6 S can
D e a th s / N
24 / 39
25 / 31
9 / 10
13 / 13
11 / 11
M e d ia n
in M o n th s
1 4 (9 , 1 8 )
8 (6 , 1 1 )
7 (4 , 1 0 )
3 (2 , 5 )
1 (1 , 1 )
60%
40%
20%
0%
0
6
12
18
24
M o n th s fro m S ta rt o f T re a tm e n t
30
Central Interpretation of Week 6
Anatomic Imaging
99 patients (available
for analysis)
80 pts with Week 6
anatomic imaging
19 pts without Week 6
anatomic imaging
51 pts with Progressive Disease
29 pts with NonProgressive disease
(SD, CR, or PR)
Progression Based On:
1) Dimension criteria by WHO (N= 30)
2) Presence of new lesions (N=9)
3) Both dimension criteria and presence of new
lesions (N=12)
Survival Using Central Interpretation
N
P
P
P
N
100%
80%
o n P r o g r e s s iv e D is e a s e
D b y D im e n s io n
D b y N e w L e s io n
D b y N e w L e s io n + D im e n s io n
o W eek 6 S can
D e a th
22 /
28 /
8 /
11 /
19 /
s
2
3
9
1
1
/ N
9
0
2
9
M e d ia n
in M o n th s
1 7 (1 3 , 1 9 )
8 (6 , 1 0 )
7 (4 , 1 0 )
5 (3 , 6 )
1 (1 , 4 )
60%
40%
20%
0%
0
12
24
36
M o n th s fro m S ta rt o f T re a tm e n t
48
Median Survival (Days)
Category
Local
Interpretation
Central
Interpretation
N
N
Median
Survival
Median
Survival
Non- Progressive
Disease
39
329
29
517
Progression by
Dimensions
31
211
30
227
Progression by
New Lesion
10
199
9
184
Progression BOTH
by Dimension
Criteria and New
Lesions
13
98
12
150
No Week 6 Scan
11
29
P < 0.01
FDG PET
Joo Hyun , Brandon S. Luber, Jeffrey P. Leal,
Hao Wang, Vanessa Bolejack, Scott M.
Schuetze, Lawrence H. Schwartz, Lee J.Helman,
Laurence H. Baker, Richard L. Wahl
Conclusions
• Progression determined by increase in size and new lesions
predicts for worse prognosis than either alone
• Central read non progression is predictive of longer survival
than local read ( 517 days vs 329 days)
• Patients who did not have image at 6 weeks had worse
survival (1 month), thus intent to treat analysis must be our
standard
• FDG PET on day 9 is strong predictor of overall survival
(ms in review)
Future Directions
• Compare RECIST and WHO criteria by central radiology
• Measure response and progression by volumetric
analysis
• Compare individual patients that were nonprogression
by CT/MR to those with partial metabolic response on
FDG PET
• Compare two “expert” central reads of PET data