Journal Article

TRIBE-2: a phase III, randomized, open-label, strategy trial in unresectable metastatic colorectal cancer patients by the GONO group

Cremolini, Chiara, Boni, Luca, Marmorino, Federica, Schirripa, Marta, Tamburini, Emiliano, Antoniotti, Carlotta, Loupakis, Fotios, Ricci, Vincenzo, Di Donato, Samantha, Ronzoni, Monica, Pietrantonio, Filippo, Santini, Daniele, Falcone, Alfredo, Lonardi, Sara, Tomasello, Gianluca, Passardi, Alessandro, Zagonel, Vittorina, Valsuani, Chiara, Aprile, Giuseppe, Salvatore, Lisa, Allegrini, Giacomo, Masi, Gianluca

2017

Overview

Background Chemotherapy plus bevacizumab is a standard first-line treatment for unresectable metastatic colorectal cancer patients. Different chemotherapy backbones may be chosen, including one to three drugs, based on patients’ general conditions and comorbidities, treatments’ objectives, and disease characteristics. TRIBE trial demonstrated a significant advantage in terms of progression-free survival and overall survival for FOLFOXIRI plus bevacizumab as compared with FOLFIRI plus bevacizumab. Based on recent evidence, the de-intensification of the upfront regimen after 4–6 months of treatment is nowadays regarded as a valuable option. Moreover, the prolonged inhibition of angiogenesis, and in particular the continuation of bevacizumab beyond the evidence of disease progression, is an efficacious strategy in the treatment of metastatic colorectal cancer patients. Methods/design TRIBE-2 is a prospective, open-label, multicentric phase III randomized trial in which unresectable and previously untreated metastatic colorectal cancer patients are randomized to receive first-line FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab after disease progression or FOLFOXIRI plus bevacizumab followed by the re-introduction of the same regimen after disease progression. The primary endpoint is to compare the efficacy of the two proposed treatment strategies in terms of Progression Free Survival 2. Discussion The TRIBE-2 study aims at answering the question whether the upfront use of FOLFOXIRI improves the clinical outcome of metastatic colorectal cancer patients, when compared with the pre-planned, sequential use of oxaliplatin-based and irinotecan-based doublets. Both proposed treatment strategies are designed to exploit the effectiveness of the prolonged inhibition of angiogenesis, alternating short (up to 4 months) induction periods and less intensive maintenance phases. Trial registration TRIBE2 is registered at Clinicaltrials.gov: NCT02339116 . January 12, 2015. TRIBE-2 is registered at EUDRACT 2014–004436-19, October 10, 2014.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Angiogenesis / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Bevacizumab / Bevacizumab - therapeutic use / Biomedical and Life Sciences / Biomedicine / Camptothecin - analogs & derivatives / Camptothecin - therapeutic use / Cancer Research / Cancer therapies / Care and treatment / Chemotherapy / Clinical trial / Clinical trials / Colorectal cancer / Colorectal Neoplasms - drug therapy / Colorectal Neoplasms - immunology / Colorectal Neoplasms - pathology / Colorectal Neoplasms - therapy / Combination chemotherapy / Comparative analysis / Diagnosis / Disease-Free Survival / Fluorouracil - therapeutic use / Folfoxiri / Health aspects / Health Promotion and Disease Prevention / Health risk assessment / Humans / Immunotherapy / Irinotecan / Leucovorin - therapeutic use / Medical and radiation oncology / Medicine/Public Health / Metastases / Metastasis / Monoclonal antibodies / Neoplasm Metastasis / Oncology / Organoplatinum Compounds - therapeutic use / Oxaliplatin / Patient outcomes / Prospective Studies / Research Design / Strategy / Studies / Study Protocol / Surgical Oncology / Survival / Targeted cancer therapy / Treatment Outcome