Updated results from TRIBE, an Italian phase III study of patients with metastatic colorectal cancer, indicate that FOLFOXIRI chemotherapy in combination with bevacizumab is superior to the standard FOLFIRI chemotherapy with bevacizumab. The study was presented at the 2015 Gastrointestinal Cancers Symposium in San Francisco, California.
Compared with the FOLFIRI combination regimen with bevacizumab, the FOLFOXIRI plus bevacizumab regimen extended overall survival by about 4 months and doubled the 5-year overall survival rate.
The study confirms findings from a previous, smaller phase III study (GONO) which showed that FOLFOXIRI alone improved survival compared with FOLFIRI alone in the first-line treatment of metastatic colorectal cancer.
“This new approach offers a substantial survival improvement, even for patients with a rather unfavorable prognosis. This is a remarkable step forward in the treatment of this disease,” said presenting author Chiara Cremolini, MD, a medical oncologist at the Tuscan Tumor Institute in Pisa, Italy. “We believe that our results will encourage clinicians to adopt the FOLFOXIRI regimen with bevacizumab as an upfront therapy option for patients in otherwise good health.”
The most widely used chemotherapy regimens for first-line treatment of colorectal cancer are FOLFOX and FOLFIRI. FOLFOXIRI contains oxaliplatin in addition to the two cytotoxic drugs contained in the FOLFIRI regimen.
In the study, 508 patients with metastatic colorectal cancer were randomly assigned to induction therapy consisting of FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab. Up to 6 months (12 cycles) of induction therapy were planned, followed by maintenance treatment with bevacizumab in combination with less intensive chemotherapy, 5-FU, until the disease progressed.
In approximately 80% of the patients, the cancer was not confined to the liver, and surgery was not feasible in most of them. Similar numbers of patients in both groups (15% in the FOLFOXIRI plus bevacizumab group, 12% in the FOLFIRI plus bevacizumab group) were able to undergo surgery (radical resection) after the induction therapy shrunk their tumors.
Patients were followed for a median period of 48.1 months. The median overall survival was significantly improved in the FOLFOXIRI plus bevacizumab group compared to the FOLFIRI plus bevacizumab group (29.8 vs. 25.8 months). An estimated 1 of every 4 patients (24.9%) in the FOLFOXIRI group was alive 5 years after starting treatment, compared with 1 of every 8 patients (12.4%) in the FOLFIRI group.
While FOLFOXIRI increased the risks of diarrhea and low blood counts compared with FOLFIRI, serious adverse events were not increased. Cremolini noted that, while many patients are able to tolerate FOLFOXIRI, it is an intensive regimen and should not be given to all patients, such as those older than 75 years and those 70 to 75 years who are not in good general condition.