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Ann Oncol. 2015 Apr;26(4):702-8. doi: 10.1093/annonc/mdu580. Epub 2014 Dec 23.

Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial.

Author information

1
Department of Surgery I, Rudolfstiftung Hospital, Vienna, Austria t.gruenberger@icloud.com.
2
Department of Oncology, University College London Cancer Institute, London.
3
Department of Medicine, The Royal Marsden Hospital, Sutton, UK.
4
Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
5
Department of Surgical Oncology, Léon Bérard Cancer Center, Université Claude Bernard Lyon I, Lyon, France.
6
Department of Surgery, The Royal Marsden Hospital, Sutton, UK.
7
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
8
Genentech, Inc., South San Francisco, USA.
9
Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, UMR-S 776, Université Paris-Sud, Villejuif, France.

Abstract

BACKGROUND:

For patients with initially unresectable liver metastases from colorectal cancer, chemotherapy can downsize metastases and facilitate secondary resection. We assessed the efficacy of bevacizumab plus modified FOLFOX-6 (5-fluorouracil/folinic acid, oxaliplatin) or FOLFOXIRI (5-fluorouracil/folinic acid, oxaliplatin, irinotecan) in this setting.

PATIENTS AND METHODS:

OLIVIA was a multinational open-label phase II study conducted at 16 centres in Austria, France, Spain, and the UK. Patients with unresectable liver metastases were randomised to bevacizumab (5 mg/kg) plus mFOLFOX-6 [oxaliplatin 85 mg/m(2), folinic acid 400 mg/m(2), 5-fluorouracil 400 mg/m(2) (bolus) then 2400 mg/m(2) (46-h infusion)] or FOLFOXIRI [oxaliplatin 85 mg/m(2), irinotecan 165 mg/m(2), folinic acid 200 mg/m(2), 5-fluorouracil 3200 mg/m(2) (46-h infusion)] every 2 weeks. Unresectability was defined as ≥1 of the following criteria: no possibility of upfront R0/R1 resection of all lesions; <30% residual liver volume after resection; metastases in contact with major vessels of the remnant liver. Resectability was evaluated by multidisciplinary review. The primary end point was overall resection rate (R0/R1/R2). Efficacy end points were analysed by intention-to-treat analysis.

RESULTS:

In patients assigned to bevacizumab-FOLFOXIRI (n = 41) or bevacizumab-mFOLFOX-6 (n = 39), the overall resection rate was 61% [95% confidence interval (CI) 45% to 76%] and 49% (95% CI 32% to 65%), respectively (difference 12%; 95% CI -11% to 36%). R0 resection rates were 49% and 23%, respectively. Overall tumour response rates were 81% (95% CI 65% to 91%) with bevacizumab-FOLFOXIRI and 62% (95% CI 45% to 77%) with bevacizumab-mFOLFOX-6. Median progression-free survival (PFS) was 18·6 (95% CI 12.9-22.3) months and 11·5 (95% CI 9.6-13.6) months, respectively. The most common grade 3-5 adverse events were neutropenia (bevacizumab-FOLFOXIRI, 50%; bevacizumab-mFOLFOX-6, 35%) and diarrhoea (30% and 14%, respectively).

CONCLUSIONS:

Bevacizumab-FOLFOXIRI was associated with higher response and resection rates and prolonged PFS versus bevacizumab-mFOLFOX-6 in patients with initially unresectable liver metastases from colorectal cancer. Toxicity was increased but manageable with bevacizumab-FOLFOXIRI.

CLINICALTRIALSGOV:

NCT00778102.

KEYWORDS:

bevacizumab; chemotherapy; colorectal cancer; liver metastases; secondary resection

PMID:
25538173
DOI:
10.1093/annonc/mdu580
[Indexed for MEDLINE]

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