FIRE-3: Cetuximab/FOLFIRI prolongs metastatic colorectal cancer survival
AT THE ASCO ANNUAL MEETING 2013
Major finding: Median overall survival with cetuximab plus FOLFIRI was 28.7 months vs. 25 months with bevacizumab plus FOLFIRI.
Data source: Multicenter, randomized phase III trial of first-line cetuximab or bevacizumab plus FOLFIRI chemotherapy in 592 patients with wild-type KRAS metastatic colorectal cancer.
Disclosures: Dr. Heinemann reported honoraria, other remuneration, and research funding from the study sponsor, Merck, and honoraria and other remuneration from Roche. Several of his coauthors reported honoraria, other remuneration, and research funding from Merck. Merck distributes cetuximab outside of the United States.
CHICAGO – Pairing cetuximab with first-line FOLFIRI chemotherapy significantly extended overall survival by roughly 4 months over bevacizumab plus FOLFIRI among patients with KRAS wild-type metastatic colorectal cancer in the phase III FIRE-3 trial.
Patients in the cetuximab (Erbitux) and bevacizumab (Avastin) arms had similar times to disease progression of 10 and 10.3 months, respectively (Hazard ratio, 1.06; P = .54), but those given cetuximab lived for 28.7 months vs. 25 months with bevacizumab (HR, 0.77; P = .017).
The German AIO (Arbeitsgemeinschaft In-ternistische Onkologie) study group trial is the first to directly compare the two approved targeted agents with FOLFIRI (folinic acid, fluorouracil, and irinotecan) chemotherapy.
"Based on our findings, we believe that a substantial gain in survival can be achieved when doctors offer cetuximab-based treatment as first-line to their patients with KRAS wild-type metastatic colorectal cancer," lead author Dr. Volker Heinemann said in a press briefing at the annual meeting of the American Society of Clinical Oncology (ASCO), where the data were presented.
FIRE-3 was a negative trial, however, as the primary end point of objective response rate was statistically similar between the cetuximab and bevacizumab arms at 62% and 57% in an intent-to-treat analysis of all 592 patients (odds ratio, 1.18; P = .18). Response was significantly greater with cetuximab though among the 526 patients assessable for efficacy (72.2% vs. 63.1%; OR, 1.52; P = .17), said Dr. Heinemann, professor of medical oncology at the University of Munich.
The take-home message is that patients with metastatic colorectal cancer have options, but the mixed results also raise questions about the influence of subsequent therapies on overall survival, Dr. Richard Goldberg, physician-in-chief at The Ohio State University’s Comprehensive Cancer Center and an ASCO spokesperson, said at the briefing.
"Really all of the different lines of therapy contributed to this outcome and I would challenge the investigators from the AIO to go back and study their data -- study the second, third and fourth-line treatments that their patients had and help explain this finding, which does seem a bit anomalous," he said.
Dr. Heinemann responded that these data will be presented at a forthcoming meeting in Barcelona, and that data suggest cetuximab-based therapy causes deeper tumor shrinkage than bevacizumab. About 60% of all patients received second-line therapy and about 40% crossed over to the other study arm, he added.