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
A partir de données issues de l'essai de phase III TRIBE évaluant l'ajout de bévacizumab à un protocole FOLFOXIRI chez des patients atteints d'un cancer colorectal métastatique, cette étude évalue l'association entre deux critères de jugement intermédiaires, la régression tumorale précoce et la profondeur de réponse, et la survie globale
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) vs FOLFIRI plus bev.
Patients and Methods : A landmark approach was adopted to define the evaluable 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%, as compared to the control arm (62.7% vs 51.9%, p=0.025). Also the DoR was significantly higher in the triplet plus bev arm (43.4% vs 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 as compared to 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 endpoint for clinical trials' design deserving further investigation.
Annals of Oncology , résumé, 2015