No Progression-Free Survival Benefit of Adding VEGF Inhibitor Cediranib to First-Line Chemotherapy in Advanced Biliary Tract Cancer
In a UK randomized phase II trial (ABC-03) reported in The Lancet Oncology, Valle et al found that adding the VEGF inhibitor cediranib to first-line cisplatin/gemcitabine did not improve progression-free survival in patients with advanced biliary tract cancer.
Study Details
In the double-blind study, 124 patients from UK centers were randomly assigned between April 2011 and September 2012 to receive cisplatin at 25 mg/m2 and gemcitabine at 1,000 mg/m2 on days 1 and 8 every 21 days for up to eight cycles plus either oral cediranib at 20 mg (n = 62) or placebo (n = 62) once daily until disease progression. The primary endpoint was progression-free survival in the intent-to-treat population.
Progression-Free Survival
Median follow-up was 12.2 months. Median progression-free survival was 8.0 months (95% confidence interval [CI] = 6.5–9.3 months) in the cediranib group vs 7.4 months (95% CI = 5.7–8.5 months) in the placebo group (hazard ratio = 0.93, P = .72). Progression-free survival at 12 months was 21.8% vs 16.1%. The objective response rate was higher in the cediranib group (44%, including complete response in 3%, vs 19%, all partial responses; P = .0036).
Grade 3 or 4 adverse events were more common in the cediranib group, including hypertension (37% vs 21%), diarrhea (13% vs 3%), thrombocytopenia (16% vs 6%), leukopenia (24% vs 11%), and fatigue (24% vs 11%).
The investigators concluded: “Cediranib did not improve the progression-free survival of patients with advanced biliary tract cancer in combination with cisplatin and gemcitabine, which remains the standard of care. Although patients in the cediranib group had more adverse events, we recorded no unexpected toxic effects. The role of VEGF inhibition in addition to chemotherapy for patients with advanced biliary tract cancer remains investigational.”
Juan W. Valle, MD, of University of Manchester and Manchester Academic Health Science Centre/The Christie NHS Foundation Trust, is the corresponding author for the Lancet Oncology article.
The study was funded by Cancer Research UK and AstraZeneca Pharmaceuticals. For full disclosures of the study authors, visit www.thelancet.com.
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