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 0.978-0.987 <0.0001 HR for OS 0.979 0.973-0.984 HR for PPS 0.987 0.982-0.993 *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 [0.52-0.79] 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 [0.49-0.73] p<0.0001 Results: ETS and DoR according to treatment arm HR for PFS 95%CI p Higher DoR 0.983 0.980-0.987 <0.0001 HR for OS 0.979 0.975-0.983 HR for PPS 0.987 0.984-0.991 DoR > median* (Died/N=110/241), mOS: 36.8 mos DoR ≤ median* (Died/N=156/243), mOS : 21.3 mos HR: 0.47 [0.35-0.58] 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 [0.39-0.67] 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 [0.47-0.81] 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 [0.44-0.73] 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 chiaracremolini@gmail.com