Metastatic Colon Cancer: Survival Improved With FOLFOXIRI and Bevacizumab

Alfredo Falcone MD Chiara Cremolini Fotios Loupakis University of Pisa and Azienda-Ospedaliero Universitaria Pisana ItalyMedicalResearch.com Interview with:
Alfredo Falcone MD
Chiara Cremolini Fotios Loupakis
University of Pisa and Azienda-Ospedaliero Universitaria Pisana
Italy

Medical Research: What are the main findings of the study?

Dr. Falcone: In the TRIBE study the main findings are that the use of an initial more intensive therapy with a triplet of cytotoxics (FOLFOXIRI) plus bevacizumab vs a doublet (FOLFIRI) + bevacizumab improves the outcome of metastatic colorectal cancer patients with unresectable metastases. In particular FOLFOXIRI + bevacizumab vs FOLFIRI+bevacizumab improved RECIST response-rate (65% vs 53%, p=0.006), progression-free survival which was the primary endpoint (median 12,1 vs 9,7 months, HR=0,75, p=0.003) and overall survival (median 31,0 vs 25,8 months, HR=0.79, p=0.054). These results, also compared to those reported in previous phase III studies in molecularly unselected patients, represent an important advance in the treatment of this disease.

Medical Research: What was most surprising about the results?

Dr. Falcone: That the improvement in the outcome with FOLFOXIRI+bevacizumab was observed despite the fact that  no improvement in the secondary R0 resection rate of metastases was observed (15% vs 12%, p=0.33). This indicates that FOLFOXIRI+bevacizumab is a more effective therapy also in a palliative setting where secondary surgery of metastases is not a reasonable objective of the treatment.

Medical Research: What should clinicians and patients take away from your report?

Dr. Falcone: To consider an initial intensive therapy with FOLFOXIRI+bevacizumab, followed by maintenance with 5-FU/LV and bevacisumab, as a very good option for many metastatic colorectal cancer patients with a good ECOG Performace-status (0-1), no relevant comorbidities and age < 70-75 yrs, independently from the molecular characteristcs of the tumor.  In patients with RAS mut or BRAF mut tumors FOLFOXIRI+bevacizumab may represent today the best option.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Falcone: First of all to update the overall survival of the TRIBE study to estimate the long-term benefit of FOLFOXIRI+bevacizumab.

In the meantime, to improve the tolerance of the regimen, and perhaps its efficacy, by reducing the duration of the induction phase from 6 to 4 months, followed by a maintenance with bevacizumab and a low toxic metronomic chemotherapy, followed by a re-treatment with FOLFOXIRI+bevacizumab at the first progression (MOMA study).

In the RAS-wt patients it is of great interest to study the triplet FOLFOXIRI in combination with anti-EGFR mAbs and also these studies are ongoing with preliminary promising results (MACBETH study).

Citation:

Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer

Fotios Loupakis, M.D., Ph.D., Chiara Cremolini, M.D., Gianluca Masi, M.D., Sara Lonardi, M.D., Vittorina Zagonel, M.D., Lisa Salvatore, M.D., Enrico Cortesi, M.D., Gianluca Tomasello, M.D., Monica Ronzoni, M.D., Rosella Spadi, M.D., Alberto Zaniboni, M.D., Giuseppe Tonini, M.D., Angela Buonadonna, M.D., Domenico Amoroso, M.D., Silvana Chiara, M.D., Chiara Carlomagno, M.D., Ph.D., Corrado Boni, M.D., Giacomo Allegrini, M.D., Luca Boni, M.D., and Alfredo Falcone, M.D.

N Engl J Med 2014; 371:1609-1618
October 23, 2014