Chiara Cremolini, MD
Intensifying the chemotherapy component of a standard first-line bevacizumab-containing regimen reduced the risk of death by about 20% and doubled the 5-year overall survival (OS) rate among patients with metastatic colorectal cancer (mCRC), according to clinical trial results that will be presented this week at the 2015 Gastrointestinal Cancers Symposium in San Francisco.1
The FOLFOXIRI chemotherapy regimen in combination with bevacizumab resulted in a median OS rate of 29.8 months compared with 25.8 months for the FOLFIRI plus bevacizumab protocol in the phase III TRIBE trial (HR = 0.80; CI, 0.65-0.98; P
= .030), researchers said during a press conference Monday in advance of the conference. After a median 48.1 months’ follow-up, an estimated one out of four patients (24.9%) in the FOLFOXIRI group was still alive, as opposed to one out of eight patients (12.4%) in the FOLFIRI group.
“FOLFOXIRI plus bevacizumab represents a new valuable option for the upfront treatment of metastatic colorectal cancer patients,” said lead author Chiara Cremolini, MD, a medical oncologist at the Tuscan Tumor Institute in Pisa, Italy. She said the advantage with the more intensive regimen “increases over time.”
However, Cremolini said, not all patients would be considered good candidates for the FOLFOXIRI regimen, which combines three chemotherapy drugs. FOLFOXIRI includes all of the elements of FOLFIRI (folinic acid [leucovorin], fluorouracil [5-FU], and irinotecan) plus oxaliplatin.
Overall, 508 patients with mCRC were randomized to receive either FOLFOXIRI plus bevacizumab (n = 252) or FOLFIRI plus bevacizumab (n = 256) for up to 12 cycles over 6 months. Some 15% of patients in the FOLFOXIRI group and 12% in the FOLFIRI cohort were able to undergo radical resection after induction therapy. Patients received follow-up 5-FU/leucovorin plus bevacizumab as maintenance therapy until disease progression.
The TRIBE trial enrolled patients between the ages of 18 years and 75 years, but individuals 70 to 75 years were eligible only with a performance status of 0, said Cremolini. “It is not recommended to administer this regimen to patients older than 75,” she said.
The FOLFOXIRI regimen has been shown to increase the incidence of grade 3/4 diarrhea, mucositis, neuropathy, and neutropenia compared with the FOLFIRI regimen, Cremolini said. She noted that participants in the TRIBE trial were generally in good condition but had a poor prognosis; many of the patients had more than one site of metastasis and most were unresectable.
Smitha S. Krishnamurthi, MD, who served as moderator of the presscast, said the TRIBE trial “clearly demonstrates” that the FOLFOXIRI plus bevacizumab regimen is safe and effective. “This regimen is not for everyone but for the right patients this is one of the most active regimens with an impressive, almost 25% survival rate at 5 years,” said Krishnamurthi, associate professor of Medicine at Case Western Reserve University in Cleveland, Ohio.
The findings presented this week are updated results from the trial, which the Gruppo Oncologico del Nord Ovest (GONO) research group conducted at 34 cancer centers throughout Italy from July 2008 through May 2011. The primary endpoint of the study was progression-free survival (PFS), a milestone that was reached 2 years ago. 2
In the updated results, the median PFS was 12.3 months with FOLFOXIRI plus bevacizumab versus 9.7 months with FOLFIRI plus bevacizumab (HR = 0.77; CI, 0.65-0.93; P
The benefits were evident across all subgroups analyzed, said Cremolini. Krishnamurthi said clinicians in the United States generally did not start using the FOLFOXIRI regimen based on the earlier results because they already were incorporating chemotherapy and bevacizumab into treatment plans. FOLFIRI is a widely used frontline therapy in the treatment of patients with mCRC, along with the FOLFOX regimen of folinic acid, 5-FU, and oxaliplatin.
The GONO group will continue its research with the phase III TRIBE-2 trial in which 654 patients will be randomized 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, researchers indicated.