Background

1. 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., BoniC., Negri F., Barone C., Vitello S., Giuntini N., Bonetti A., D’Amico M., BoniL., Falcone A. Onbehalf of the GONO (Gruppo Oncologico del Nord Ovest, Italy) investigators Results: ETS correlates with PFS, OS and PPS Background TRIBE – study design Results: DoR correlates with PFS, OS and PPS Results: Analyses as continuous variables • Phase III TRIBE trial demonstratedthat FOLFOXIRI plus bevprovides a significantadvantage 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 showedthat • the anti-EGFR cetuximabwasable to increase the ETS, thatwassignificantlyassociated with PFS and OS (more evidently in the chemotherapy plus cetuximabarm) • Piessevauxet al, J ClinOncol 2013 • the anti-EGFR cetuximabwasable to increase the DoR, thatwassignificantlyassociated with post-progressionsurvival (PPS) and OS • Mansmannet al, ASCO GI 2013 • both ETS and DoRmay be regardedasvaluablepredictors of clinicaloutcome to be furtherinvestigated. *MedianDoR: 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 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 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 + bevallows to achieve an higherearlyresponse rate and a betterextent of DoRcomparedto FOLFIRI + bev. ETS predicts PFS, PPS and OS also in patientstreated with chemotherapy + bev, thusconfirming the importance of achieving an earlyresponse in order to improve long-termprognosis. DoRsignificantlycorrelates with PPS and OS, aspreviouslydemonstrated with chemotherapy + cetuximab, butalso with PFS. These data confirm the value of both ETS and DoRasdeterminants of long-termoutcome and potentialendpoints for clinical trials. *65 patientswerenotevaluable for ETS EarlyTumorShrinkage (ETS): relative change in the sum of the longestdiameters of RECIST target lesionsat week 8 compared to baseline. Cut-off value: 20%. Piessevaux et al, JClinOncol 2013 Deepness of Response (DoR): relative change in the sum of the longestdiameters of RECIST target lesionsat the nadir in the absence of new lesions or progression of non-target lesionscompared to baseline. Exploratorycut-off: medianDoR in evaluablepatients. 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 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 *24 patientswerenotevaluable for DoR chiaracremolini@gmail.com