Originally published as JCO Early Release 10.1200/JCO.2008.20.0238 on March 23 2009

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Phase III Trial of Bevacizumab in Combination With Gemcitabine and Erlotinib in Patients With Metastatic Pancreatic Cancer

From the University Hospital Gasthuisberg, Leuven; St-Luc University Hospital; Erasme University Hospital, Brussels, Belgium; Deventer Hospital, Deventer, the Netherlands; Centre René Gauducheau, Saint Herblain, France; British Columbia Cancer Agency, Vancouver, British Columbia; Princess Margaret Hospital, Toronto, Ontario, Canada; Medical University, Vienna, Austria; and F. Hoffmann-La Roche, Basel, Switzerland.

Corresponding author: Professor Eric Van Cutsem, MD, PhD, University Hospital Gasthuisberg/Leuven, Digestive Oncology Unit, Herestraat 49, B-3000 Leuven, Belgium; e-mail: eric.vancutsem{at}uz.kuleuven.ac.be.

Purpose Treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the rationale for a phase III trial of gemcitabine-erlotinib plus bevacizumab or placebo.

Patients and Methods Patients with metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine (1,000 mg/m²/week), erlotinib (100 mg/day), and bevacizumab (5 mg/kg every 2 weeks) or gemcitabine, erlotinib, and placebo in this double-blind, phase III trial. Primary end point was OS; secondary end points included progression-free survival (PFS), disease control rate, and safety.

Results A total of 301 patients were randomly assigned to the placebo group and 306 to the bevacizumab group. Median OS was 7.1 and 6.0 months in the bevacizumab and placebo arms, respectively (hazard ratio [HR], 0.89; 95% CI, 0.74 to 1.07; P = .2087); this difference was not statistically significant. Adding bevacizumab to gemcitabine-erlotinib significantly improved PFS (HR, 0.73; 95% CI, 0.61 to 0.86; P = .0002). Treatment with bevacizumab plus gemcitabine-erlotinib was well tolerated: safety data did not differ from previously described safety profiles for individual drugs.

Conclusion The primary objective was not met. The addition of bevacizumab to gemcitabine-erlotinib did not lead to a statistically significant improvement in OS in patients with metastatic pancreatic cancer. PFS, however, was significantly longer in the bevacizumab group compared with placebo. No unexpected safety events were observed from adding bevacizumab to gemcitabine-erlotinib.

Supported by Hoffman-La Roche.

The data shown in this paper were presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

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