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Clinical Trial
. 2015 Jun;26(6):1188-1194.
doi: 10.1093/annonc/mdv112. Epub 2015 Feb 23.

Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest

C Cremolini  1 , F Loupakis  1 , C Antoniotti  1 , S Lonardi  2 , G Masi  1 , L Salvatore  1 , E Cortesi  3 , G Tomasello  4 , R Spadi  5 , A Zaniboni  6 , G Tonini  7 , C Barone  8 , S Vitello  9 , R Longarini  10 , A Bonetti  11 , M D'Amico  12 , S Di Donato  13 , C Granetto  14 , L Boni  15 , A Falcone  16
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Free article
Clinical Trial

Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest

C Cremolini et al. Ann Oncol. 2015 Jun.
Free article

Abstract

Background: Early tumor shrinkage (ETS) and depth of response (DoR) predict overall survival (OS) in first-line trials of chemotherapy ± anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). These associations and the predictive accuracy of response measurements for survival parameters were investigated in the phase III TRIBE trial of FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev.

Patients and methods: A landmark approach was adopted to define the assessable population. The distribution of RECIST response rate, ETS and DoR was compared in the two arms. Associations between response measurements and progression-free survival (PFS), post-progression survival (PPS) and OS were tested by univariate and multivariate Cox models. Prediction performance of each factor was estimated by C-index.

Results: A significantly higher percentage of patients in the FOLFOXIRI plus bev arm achieved ETS ≥20%, when compared with the control arm (62.7% versus 51.9%, P = 0.025). Also the DoR was significantly higher in the triplet plus bev arm (43.4% versus 37.8%, P = 0.003). Both ETS and DoR were associated with PFS, PPS and OS at the univariate analyses and in the multivariate models stratified for other prognostic variables. Both ETS and DoR were able to predict survival as accurately as RECIST response.

Conclusion: FOLFOXIRI plus bev improves ETS and DoR when compared with FOLFIRI plus bev. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus bev. ETS is a promising and valuable end point for clinical trials' design deserving further investigation.

Trial registration: ClinicalTrials.gov NCT00719797.

Keywords: FOLFOXIRI; bevacizumab; depth of response; early tumor shrinkage.

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