1. results from the phase III TRIBE trial
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
Background
TRIBE – study design
Results: ETS correlates with PFS, OS and PPS
Results: DoR correlates with PFS, OS and PPS
Results: Analyses as continuous variables
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
Results from CRYSTAL and OPUS trial showed that
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
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
both ETS and DoR may be regarded as valuable predictors of clinical outcome to be further investigated.
HR for PFS
95%CI p
Higher ETS
0.983
<0.0001
HR for OS
0.979
HR for PPS
0.987
*Median DoR: 38.9%
ETS > 20% (Progr/N=208/256), mPFS: 12.7 mos
ETS ≤ 20% (Progr/N=171/187), mPFS : 10.0 mos
HR: 0.66 [ ]
p<0.0001
DoR > median* (Progr/N=201/241), mPFS: 13.1 mos
DoR ≤ median* (Progr/N=217/243), mPFS : 9.3 mos
HR: 0.61 [ ]
p<0.0001
Results: ETS and DoR according to treatment arm
HR for PFS
95%CI p
Higher DoR
0.983
<0.0001
HR for OS
0.979
HR for PPS
0.987
DoR > median* (Died/N=110/241), mOS: 36.8 mos
DoR ≤ median* (Died/N=156/243), mOS : 21.3 mos
HR: 0.47 [ ]
p<0.0001
N=443*
FOLFIRI + bev
Arm A
N = 222
FOLFOXIRI + bev
Arm B
N = 221 p
Range
-100%/+56.9%
-100%/+54.5%
Median
-21.4%
-30.2%
<0.0001
ETS > 20%
114 (51%)
142 (64%)
ETS ≤ 20%
108 (49%)
79 (36%)
0.006
ETS > 20% (Died/N=118/256), mOS: 35.8 mos
ETS ≤ 20% (Died/N=120/187), mOS : 22.4 mos
HR: 0.54 [ ]
p<0.0001
Both ETS and DoR correlate with PFS, PPS and OS irrespectively of the treatment arm.
Conclusions
Definitions
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.
*65 patients were not evaluable for ETS
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%.
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 cut-off: median DoR in evaluable patients.
ETS > 20% (Died/N=118/208), mPPS: 17.1 mos
ETS ≤ 20% (Died/N=120/171), mPPS : 10.7 mos
HR: 0.64 [ ]
p=0.0005
DoR > median* (Died/N=110/201), mPPS: 18.4 mos
DoR ≤ median* (Died/N=156/217), mPPS: 10.5 mos
HR: 0.58 [ ]
p<0.0001
N=484*
FOLFIRI + bev
Arm A
N = 245
FOLFOXIRI + bev
Arm B
N = 239 p
Range
-100%/+56.9%
-100%/+54.5%
Median
-33.8%
-42.2%
0.0009
*24 patients were not evaluable for DoR