ASCO_GI_2014_files/Cremolini TRIBE ETS_DoR poster ASCO GI

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Early Tumor Shrinkage (ETS) and Deepness of Response (DoR) predict Progression Free, Post-Progression and Overall Survival:
results from the phase III TRIBE trial
Cremolini C., Loupakis F., Antoniotti C., Masi G., Lonardi S., Trenta P., Tomasello G., Ronzoni M., Ciuffreda L., Zaniboni A., Carlomagno C., Boni C., Negri F., Barone C., Vitello S., Giuntini N., Bonetti A., D’Amico M., Boni L., Falcone A.
On behalf of the GONO (Gruppo Oncologico del Nord Ovest, Italy) investigators
TRIBE – study design
Background
Results: ETS correlates with PFS, OS
and PPS
 Phase III TRIBE trial demonstrated that FOLFOXIRI plus
bev provides a significant advantage in terms of PFS,
RECIST response, and OS as compared to FOLFIRI plus
bev.
Falcone et al, ASCO Ann Meet 2013
Early Tumor Shrinkage (ETS): relative change in the sum
of the longest diameters of RECIST target lesions at week
8 compared to baseline. Cut-off value: 20%.
[email protected]
HR: 0.66 [0.52-0.79]
p<0.0001
50
25
0
0
10
20
30
40
50
100
DoR > median* (Progr/N=201/241), mPFS: 13.1 mos
DoR ≤ median* (Progr/N=217/243), mPFS : 9.3 mos
75
HR: 0.61 [0.49-0.73]
p<0.0001
50
-100%/+56.9%
-100%/+54.5%
Median
-21.4%
-30.2%
ETS > 20%
114 (51%)
142 (64%)
ETS ≤ 20%
108 (49%)
79 (36%)
p
<0.0001
0.006
75
25
*65 patients were not evaluable for ETS
N=484*
FOLFIRI + bev
Arm A
N = 245
FOLFOXIRI + bev
Arm B
N = 239
Range
-100%/+56.9%
-100%/+54.5%
Median
-33.8%
-42.2%
*24 patients were not evaluable for DoR
HR: 0.54 [0.39-0.67]
p<0.0001
50
0
0
0
10
20
30
10
20
30
p
40
50
0.0009
25
0
0
10
20
30
Months
40
50
60
95%CI
p
0.983
0.978-0.987
<0.0001
HR for OS
95%CI
p
0.979
0.973-0.984
<0.0001
HR for PPS
95%CI
p
0.987
0.982-0.993
<0.0001
HR for PFS
95%CI
p
0.983
0.980-0.987
<0.0001
HR for OS
95%CI
p
0
10
100
20
30
40
50
60
DoR > median* (Died/N=110/201), mPPS: 18.4 mos
DoR ≤ median* (Died/N=156/217), mPPS: 10.5 mos
75
HR: 0.58 [0.44-0.73]
p<0.0001
50
25
0
Higher DoR
0.979
0.975-0.983
<0.0001
HR for PPS
95%CI
p
Higher DoR
0.987
0.984-0.991
<0.0001
Both ETS and DoR correlate with PFS, PPS and OS
irrespectively of the treatment arm.
Conclusions
25
Months
HR: 0.64 [0.47-0.81]
p=0.0005
50
Higher DoR
60
50
60
ETS > 20% (Died/N=118/208), mPPS: 17.1 mos
ETS ≤ 20% (Died/N=120/171), mPPS : 10.7 mos
75
50
HR: 0.47 [0.35-0.58]
p<0.0001
75
Months
100
40
DoR > median* (Died/N=110/241), mOS: 36.8 mos
DoR ≤ median* (Died/N=156/243), mOS : 21.3 mos
100
0
0
Higher ETS
Months
ETS > 20% (Died/N=118/256), mOS: 35.8 mos
ETS ≤ 20% (Died/N=120/187), mOS : 22.4 mos
100
Higher ETS
HR for PFS
25
60
Percent survival
FOLFOXIRI + bev
Arm B
N = 221
Range
Piessevaux et al, J Clin Oncol 2013
Deepness of Response (DoR): relative change in the sum
of the longest diameters of RECIST target lesions at the
nadir in the absence of new lesions or progression of
non-target lesions compared to baseline. Exploratory cutoff: median DoR in evaluable patients.
75
Percent post-Progression survival
Definitions
N=443*
FOLFIRI + bev
Arm A
N = 222
Percent survival
both ETS and DoR may be regarded as valuable
predictors of clinical outcome to be further
investigated.
ETS > 20% (Progr/N=208/256), mPFS: 12.7 mos
ETS ≤ 20% (Progr/N=171/187), mPFS : 10.0 mos
Months
the anti-EGFR cetuximab was able to increase the DoR,
that was significantly associated with post-progression
survival (PPS) and OS
Mansmann et al, ASCO GI 2013
•
Results: ETS and DoR according to
treatment arm
100
Percent Free of Progression
Percent Free of Progression
Higher ETS
Percent post-progression survival
•
the anti-EGFR cetuximab was able to increase the ETS,
that was significantly associated with PFS and OS
(more evidently in the chemotherapy plus cetuximab
arm)
Piessevaux et al, J Clin Oncol 2013
Results: Analyses as continuous
variables
*Median DoR: 38.9%
 Results from CRYSTAL and OPUS trial showed that
•
Results: DoR correlates with PFS, OS
and PPS
0
10
20
30
Months
40
50
60
FOLFOXIRI + bev allows to achieve an higher early
response rate and a better extent of DoR compared to
FOLFIRI + bev.
ETS predicts PFS, PPS and OS also in patients treated
with chemotherapy + bev, thus confirming the
importance of achieving an early response in order to
improve long-term prognosis.
DoR significantly correlates with PPS and OS, as
previously demonstrated with chemotherapy +
cetuximab, but also with PFS.
These data confirm the value of both ETS and DoR as
determinants of long-term outcome and potential
endpoints for clinical trials.

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