Background: Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose ([18F]FDG)-PET correlate with clinical outcome. Methods: Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m2 (10 mg/m2 per min) and oxaliplatin 85 mg/m2 (2-h infusion). [18F]FDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00361231. Findings: 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7·0 months (95% CI 5·3-10·3), and PFS at 6 months was 63% (47-79), which was below the targeted rate of 70%. Grade 3-4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). [18F]FDG-PET scans showed a significant decrease in maximum standardised uptake value (SUVmax) after two cycles of treatment (5·72 [SD 2·01] at baseline; 3·73 [SD 1·88] after two cycles; pmax was a significant predictor of PFS (HR 1·35, 1·14-1·60, p=0·0006) and overall survival (1·25, 1·05-1·50, p=0·01). Interpretation: GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUVmax on [18F]FDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival. Funding: Genentech Oncology and Sanofi-Aventis.
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