Patients with advanced colorectal cancer who underwent first-line treatment with bevacizumab plus FOLFOXIRI chemotherapy demonstrated significantly improved survival compared with those treated with bevacizumab plus standard FOLFIRI chemotherapy, according to updated phase 3 study results presented at the Gastrointestinal Cancers Symposium.
The bevacizumab–FOLFOXIRI combination reduced the risk for death by about 20% and also doubled the rate of 5-year survival, results showed.
The TRIBE trial included 508 patients with metastatic colorectal cancer. Cancer had spread beyond the liver in approximately 80% of patients.
“The TRIBE trial demonstrated that first-line FOLFOXIRI plus bevacizumab as compared to FOLFIRI plus bevacizumab significantly improved the PFS of metastatic colorectal cancer patients, and a significant improvement in the response rate was also observed,” Chiara Cremolini, MD, medical oncologist at the Tuscan Tumor Institute in Pisa, Italy, said during a press conference. “At the time of that analysis, OS results were still preliminary. In fact, at median follow-up of 32.2 months, only 56% of death events had been recorded.”
Cremolini and colleagues randomly assigned 252 patients to bevacizumab (Avastin, Genentech) plus FOLFOXIRI, which consists of fluorouracil, leucovorin, irinotecan and oxaliplatin. The other 256 patients received bevacizumab plus FOLFIRI, which consists of fluorouracil, leucovorin and irinotecan.
Both regimens were administered for up to 12 cycles followed by maintenance therapy with 5-FU plus bevacizumab until disease progression. Fifteen percent of patients in the FOLFOXIRI arm and 12% of patients in the FOLFIRI arm underwent surgery after induction therapy shrunk their tumors, but surgery was not feasible for the majority of patients.
Updated analysis, performed after median follow-up of 48.1 months, showed patients assigned bevacizumab plus FOLFOXIRI demonstrated significantly improved OS (29.8 months vs. 25.8 months; HR=0.8; 95% CI, 0.65-0.98).
The benefit associated with FOLFOXIRI appeared to increase over time, Cremolini said.
A higher percentage of patients assigned bevacizumab plus FOLFOXIRI were alive at 3 years (40% vs. 34.5%), 4 years (27.3% vs. 22.9%) and 5 years (24.9% vs. 12.4%).
Univariate analysis showed several factors negatively affected prognosis. Those factors included ECOG performance status of 1 or 2, synchronous metastases, disease not confined to the liver, right-sided primary tumor, unresected primary tumor and high Kohne score. When researchers used an exploratory model to account for these variables, they calculated an adjusted HR for OS of 0.77 (95% CI, 0.61-0.96).
Patients assigned to the FOLFOXIRI regimen demonstrated higher rates of diarrhea and low blood counts. However, rates of serious adverse events were comparable between treatment arms.
Although the majority of patients are able to tolerate the FOLFOXIRI regimen, it is intensive and should not be given to all patients. It should not be used for patients aged 75 years and older, or for those who are aged 70 to 75 years who are not in good general condition, according to researchers.
“The updated results of the TRIBE study demonstrated that first-line FOLFOXIRI plus bevacizumab significantly improved the survival of metastatic colorectal cancer patients as compared to FOLFIRI plus bevacizumab with a reduction in the risk for death of 20%,” Cremolini said. “Based on these results, FOLFOXIRI plus bevacizumab represents a new valuable option for the upfront treatment of metastatic colorectal cancer patients.”
For more information:
Cremolini C. Abstract #657. Presented at: Gastrointestinal Cancers Symposium; Jan. 16-18, 2015; San Francisco.
Disclosure: The researchers report consultant/advisory roles with, speakers’ bureau roles with or research funding from Amgen, Bayer, Celgene, Eli Lilly, GlaxoSmithKline, Ipsen, Italfarmco, Merck Serono, Novartis, Roche and Sanofi. See the study for a full listing of disclosures. A research grant was provided by F. Hoffmann-La Roche.