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

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

doi:10.1186/s12885-017-3360-z

Abstract

BackgroundChemotherapy 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/designTRIBE-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.DiscussionThe 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 registrationTRIBE2 is registered at Clinicaltrials.gov: NCT02339116. January 12, 2015. TRIBE-2 is registered at EUDRACT 2014–004436-19, October 10, 2014.

Highlights

Chemotherapy plus bevacizumab is a standard first-line treatment for unresectable metastatic colorectal cancer patients
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 induction periods and less intensive maintenance phases

Summary

Discussion

Results from the TRIBE study [6] clearly underlined the role of FOLFOXIRI plus bev as upfront option for unresectable mCRC patients, confirming the superiority of the triplet over the doublet FOLFIRI when bev is added to both regimens. In order to shorten the duration of combination treatments and to exploit the progression delaying ability of bev-based maintenance, combination regimens are restricted to short induction periods (4 months instead of 6 months previously adopted in the TRIBE study) followed by maintenance with fluoropyrimidine plus bev until tumor progression Another phase II study by the GONO group, named MOMA (NCT02271464), recently evaluated the efficacy of a 4 months induction treatment with the triplet plus bev, followed by maintenance.

Background

Methods/design

Findings