Preoperative FOLFOXIRI plus Bevacizumab Feasible in Colorectal Liver Metastases

The phase II OLIVIA trial compares response to pre-surgery FOLFOXIRI–bevacizumab with modified FOLFOX-6–bevacizumab in colorectal cancer patients with unresectable hepatic metastases

medwireNews: Research suggests that in patients with colorectal cancer who have initially unresectable liver metastases, treatment with FOLFOXIRI plus bevacizumab improves resection and response rates compared with a modified FOLFOX-6 (mFOLFOX-6) plus bevacizumab regimen.

The phase II OLIVIA trial enrolled colorectal cancer patients with hepatic metastases that were considered unresectable based on meeting one or more of the following criteria: upfront R0 or R1 resection of all hepatic lesions is not possible; less than 30% estimated residual liver after resection; and metastases in contact with major vessels of the remnant liver.

The overall resection rate was 61% in the 41 participants who were randomly assigned to receive open-label, preoperative FOLFOXIRI (5-fluorouracil , leucovorin, oxaliplatin and irinotecan ) together with bevacizumab. This compared with a resection rate of 49% in the 39 patients who were treated with the mFOLFOX-6 (5-fluorouracil, leucovorin and oxaliplatin ) and bevacizumab combination prior to surgery.

And R0 resection was significantly higher for patients given the FOLFOXIRI combination than those given mFOXFOX-6-based treatment, at 49% versus 23%.

FOLFOXIRI plus bevacizumab also led to a higher overall response rate than mFOLFOX-6 plus bevacizumab, at 81% and 62%, respectively. Complete response was achieved by 54% of patients who were given FOLFOXIRI and by 23% who received mFOLFOX-6.

Median progression-free survival was significantly longer in the FOLFOXIRI-based treatment group at 18.6 months versus 11.5 months in the mFOLFOX-6-based treatment group.

Neutropenia, diarrhoea and febrile neutropenia were the most common grade 3 or higher adverse events in both treatment groups, but these toxicities were observed in more patients in the FOLFOXIRI than the mFOLFOX-6 arm, at 50%, 30% and 13% versus 35%, 14% and 8%, respectively.

The team led by Thomas Gruenberger, from Rudolfstiftung Hospital in Vienna, Austria, cautions that the analyses are exploratory, not confirmatory, but add that “the trends in favour of the bevacizumab-FOLFOXIRI combination are consistent for all endpoints.”

They conclude in the Annals of Oncology: “Our findings support the feasibility of the addition of irinotecan to FOLFOX in combination with bevacizumab, which offers an effective treatment option in patients with initially unresectable [colorectal liver metastases] and may allow them to progress to surgery.”


Gruenberger T, Bridgewater J, Chau I, et al. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol; Advance online publication 23 December 2014. doi:10.1093/annonc/mdu580

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