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.

Compared to the FOLFIRI combination regimen with bevacizumab, the FOLFOXIRI plus bevacizumab regimen extended overall survival by about four months and doubled the five-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.

The study was presented at the 2015 Gastrointestinal Cancers Symposium in San Francisco.

“This new approach offers a substantial survival improvement, even for patients with a rather unfavourable 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 (folinic acid [leucovorin], fluorouracil [5-FU], oxaliplatin) and FOLFIRI (folinic acid, fluorouracil, and irinotecan).

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 initial (induction) therapy consisting of FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab.

Up to six 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 about 80 percent 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 percent in the FOLFOXIRI plus bevacizumab group, 12 percent in the FOLFIRI plus bevacizumab group) were able to undergo surgery (radical resection) after the induction therapy shrunk their tumours.

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).

One out of four patients (24.9 percent) in the FOLFOXIRI group were estimated to be alive five years after starting treatment, compared with one out of eight patients (12.4 percent) in the FOLFIRI group.

While FOLFOXIRI increased the risks of diarrhoea and low blood counts compared to FOLFIRI, serious adverse events were not increased.

Dr 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 and those between 70 and 75 who are not in good general condition.

TRIBE-2, the follow-on phase III trial to the current study, is being launched in Italy by the GONO group.

Six hundred and fifty-four patients will be randomised to receive first-line FOLFOXIRI plus bevacizumab followed by either reintroduction of FOLFOXIRI plus bevacizumab at disease progression or FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab at progression.

Ongoing phase II trials, named MACBETH and MOMA, are exploring strategies to shorten the duration of initial chemotherapy (from six to four months) and improve efficacy of the maintenance treatment.

In the MACBETH study FOLFOXIRI is being tested in combination with the targeted drug cetuximab, which works differently than bevacizumab.

Source: ASCO