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Thématique :
- Cancer colorectal (CCR)
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| Doit faire évoluer notre pratique : |
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Dans certains cas
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Nom du veilleur :
Professeur David TOUGERON
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Annals of oncology
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2015/06
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2015 Jun;26(6):1188-94
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doi: 10.1093/annonc/mdv112
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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
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Cremolini C, Loupakis F, Antoniotti C, Lonardi S, Masi G, Salvatore L, Cortesi E, Tomasello G, Spadi R, Zaniboni A, Tonini G, Barone C, Vitello S, Longarini R, Bonetti A, D'Amico M, Di Donato S, Granetto C, Boni L, Falcone A
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http://www.ncbi.nlm.nih.gov/pubmed/25712456
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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.
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Plusieurs analyses rétrospectives d’essais prospectifs ont démontré l’intérêt des paramètres « early tumor shrinkage » (diminution de plus de 20% de la masse tumorale à 8 semaines) et « depth of response » (profondeur de la réponse) pour évaluer la survie globale dans le cancer colorectal métastatique (CCRm) traité par anti-EGFR. Cette étude analyse ces paramètres dans l’essai de phase III TRIBE qui a démontré la supériorité du schéma FOLFOXIRI plus bévacizumab par rapport au FOLFIRI bévacizumab.
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Le FOLFOXIRI plus bévacizumab est supérieur au FOLFIRI plus bévacizumab en terme de « early tumor shrinkage » et de « depth of response ». Ces deux critères sont également prédictifs de la survie sans progression et de la survie globale.
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Cette étude confirme à nouveau l’intérêt d’utiliser l’« early tumor shrinkage » et la « depth of response » pour évaluer le pronostic des CCRm quelque soit la chimiothérapie ou la thérapie ciblée utilisée. L’utilisation de ces critères pour définir la stratégie thérapeutique (notamment chimiothérapie de 2ème ligne, résection secondaire et traitement de maintenance) doit être validée par des études prospectives.
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