O-006 - FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as initial treatment for metastatic colorectal cancer (TRIBE study): updated survival res...

Date 04 July 2015
Event WorldGI 2015
Session Oral and LBA abstracts
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter C. Cremolini
Citation Annals of Oncology (2015) 26 (suppl_4): 108-116. 10.1093/annonc/mdv235
Authors C. Cremolini1, S. Lonardi1, C. Barone2, A. Falcone1, M. Schirripa1, F. Loupakis1, L. Salvatore1, C. Antoniotti1, M. Ronzoni3, A. Zaniboni4, G. Tonini5, G. Masi1, S. Chiara6, C. Carlomagno7, M. Banzi8, F.V. Negri9, L. Marcucci10, G. Fontanini1, N. Borrelli1, M. Giordano1, E. Macerola1, L. Boni11
  • 1Istituto Toscano Tumori, Pisa/IT
  • 2Catholic University of Sacred Heart - Rome, Rome/IT
  • 3Istituto Scientifico San Raffaele, Milano/IT
  • 4Casa di Cura Poliambulanza, Brescia/IT
  • 5Università Campus Bio-Medico, Rome/IT
  • 6IRCSS Azienda Ospedaliero-Universitaria S. Martino-IST, Genova/IT
  • 7Azienda Ospedaliera Universitaria Federico II, Napoli/IT
  • 8Nuova Azienda Ospedaliera, Reggio Emilia/IT
  • 9University Hospital of Parma, Parma/IT
  • 10Azienda USL-5 Istituto Toscano Tumori, Pontedera/IT
  • 11Istituto Toscano Tumori, Firenze/IT

Abstract

Introduction

The phase III TRIBE study met its primary endpoint by demonstrating that first-line FOLFOXIRI plus bev significantly prolongs PFS, as compared to FOLFIRI plus bev (Loupakis et al, N Eng J Med 2014). At a median follow-up of 32.2 months a preliminary OS analysis indicated a borderline OS improvement with FOLFOXIRI plus bev (HR: 0.79, p = 0.054) with a consistent effect across RAS (KRAS and NRAS codons 12, 13, 61) and BRAF V600E molecular subgroups.

Methods

508 patients were randomized to either FOLFIRI plus bev (Arm A, N = 256) or FOLFOXIRI plus bev (Arm B, N = 252). On available samples from RAS and BRAF wild-type (wt) patients (N = 129), also KRAS and NRAS codons 59, 117 and 146 were analysed by means of Sequenom® MassArray, identifying a new “all wt” population (N = 93).

Results

At a median follow-up of 48.1 months, in the intention-to-treat population, updated median OS for Arm B vs Arm A was 29.8 vs 25.8 months (HR = 0.80, 95%CI, 0.65-0.98, p = 0.030). Notably an estimated 5-years OS rate for Arm B of 24.9% vs 12.4% in Arm A. Molecular results were informative for 357 patients (70.3%). All wt patients had significantly longer OS as compared to RAS mutant (HR = 0.70, p = 0.006) and to BRAF mutant (HR = 0.24, p < 0.001). The benefit from FOLFOXIRI plus bev was consistent across all molecular subgroups (Table 1). All wt patients treated with FOLFOXIRI plus bev reported a median OS of 41.7 months as compared to 33.5 months in the FOLFIRI plus bev group (HR = 0.75, 95%CI, 0.45-1.24).

Conclusion

FOLFOXIRI plus bev significantly improves survival of metastatic colorectal cancer patients and the OS advantage increases over time. Benefit from FOLFOXIRI plus bev is independent of RAS and BRAF mutational status. All wt patients have a better outcome independently from the treatment arm. Notable results with FOLFOXIRI plus bev are achieved in all wt patients.

Table: O-006