Gemcitabine plus a platinum agent is standard treatment in advanced biliary cancer. In the phase II open-label noncomparative BINGO trial, reported in The Lancet Oncology, Malka et al found no apparent benefit of adding the EGFR inhibitor cetuximab (Erbitux) to gemcitabine/oxaliplatin in first-line treatment in this setting.
In the trial, 150 patients with locally advanced (nonresectable) or metastatic cholangiocarcinoma, gallbladder carcinoma, or ampullary carcinoma and WHO performance status of 0 or 1 from 18 hospitals in France and Germany were randomly assigned between October 2007 and December 2009 to receive first-line treatment with gemcitabine at 1,000 mg/m² and oxaliplatin at 100 mg/m² with (n = 76) or without (n = 74) cetuximab at 500 mg/m² every 2 weeks.
Randomization was stratified by center, primary disease site, disease stage, and previous treatment with curative intent or adjuvant therapy. The primary endpoint was proportion of patients who were progression-free at 4 months in the intention-to-treat population.
The cetuximab and chemotherapy groups were generally balanced for age (median, 61 and 62 years), sex (57% men in both), primary disease site (eg, cholangiocarcinoma in 82% in both, including intrahepatic in 64% and 62%, gallbladder in 14% and 15%), stage (metastatic in 78% and 80%), WHO performance status (0 in 46% and 36%, 1 in 47% and 57%), previous treatment (eg, curative intent surgery in 24% and 22%, biliary stenting in 20% and 23%), and cancer antigen 19-9 level (median, 105 and 166 U/mL).
At 4 months, 48 patients in the cetuximab-plus-chemotherapy group (63%, 95% confidence interval [CI] = 52%–74%) and 40 patients in the chemotherapy group (54%, 95% CI = 43%–65%) were progression-free. Median progression-free survival was 6.1 months (95% CI = 5.1–7.6 months) and 5.5 months (95% CI = 3.7–6.6 months). Median overall survival was 11.0 months (9.1–13.7 months) and 12.4 months (8.6–16.0 months). Response occurred in 24% and 23% of patients.
Treatment after progression occurred in 42% of patients in the cetuximab group and 38% of those in the chemotherapy group, including fluorouracil or capecitabine in 72% and 43% and irinotecan in 25% and 14% of these patients.
The most common grade 3 or 4 adverse events in the cetuximab-plus-chemotherapy group were peripheral neuropathy (24% vs 15% in the chemotherapy group), neutropenia (22% vs 16%), and increased aminotransferase concentrations (22% vs 15%). Treatment-related serious adverse events occurred in 25% of the cetuximab group and in 17% of the chemotherapy group. Adverse events led to discontinuation of study treatment in 16% vs 11%. One patient in the chemotherapy group died of treatment-related atypical pneumonia.
The investigators concluded, “The addition of cetuximab to gemcitabine and oxaliplatin did not seem to enhance the activity of chemotherapy in patients with advanced biliary cancer, although it was well tolerated. Gemcitabine and platinum-based combination should remain the standard treatment option.”
David Malka, MD, of the Institut Gustave Roussy, is the corresponding author for The Lancet Oncology article.
The study was funded by Institut National du Cancer and Merck Serono. For full disclosures of the study authors, visit www.thelancet.com.
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