title: Should combination chemotherapy serve as the backbone in clinical trials of advanced pancreatic cancer? A pooled analysis of phase II trials of gemcitabine-containing doublets plus bevacizumab.
abstract: OBJECTIVE
  The objective of this study was to evaluate whether building upon multidrug chemotherapy regimens represents a viable strategy in pancreatic cancer clinical trial design.
  
  
  METHODS
  We performed a pooled analysis of all single-arm phase II studies in which a specific targeted agent (the anti-vascular endothelial growth factor monoclonal antibody bevacizumab) was added to gemcitabine-based cytotoxic doublets. The primary end point was overall survival (OS). Secondary end points included objective response rate, CA-19-9 biomarker response rate, and adverse event frequencies. Kaplan-Meier methods estimated time-to-event end points, whereas the Cox proportional hazard model estimated univariate hazard ratios of death.
  
  
  RESULTS
  For the 300 patients included in the pooled analysis, median OS was 9.1 months (95% confidence interval, 8.3-10.2). Differences in OS were observed according to patients' baseline performance status (median OS, 10.4 vs 8.6 months for Eastern Cooperative Oncology Group 0 vs 1, respectively). Moreover, bevacizumab-related adverse events were not observed at increased frequency with gemcitabine-based doublets compared with historic data.
  
  
  CONCLUSIONS
  Recognizing the limitations of cross-study comparisons, these results compare favorably to those from Cancer and Leukemia Group B 80303, a phase III trial testing bevacizumab in combination with gemcitabine alone. This is the largest data set available to demonstrate the feasibility of building upon more intensive chemotherapy backbones in clinical trials of novel targeted agents in pancreatic cancer.
authors.affiliation: From the *Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA; †Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; ‡Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY; §Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA; ∥Division of Medical Oncology, College of Medicine, The Ohio State University Medical Center, Columbus, OH; ¶Division of Biomedical Statistics and Informatics, Health Sciences Research Department, The Mayo Clinic, Rochester, MN; and #Division of Hematology and Oncology, The Mayo Clinic, Jacksonville, FL.
authors.forename: Katherine
authors.initials: K
authors.lastname: Van Loon
authors.forename: Anne M
authors.initials: AM
authors.lastname: Espinoza
authors.forename: David R
authors.initials: DR
authors.lastname: Fogelman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.forename: Milind M
authors.initials: MM
authors.lastname: Javle
authors.forename: Renuka V
authors.initials: RV
authors.lastname: Iyer
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Picozzi
authors.forename: Ludmila Katherine
authors.initials: LK
authors.lastname: Martin
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tempero
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Foster
authors.forename: George P
authors.initials: GP
authors.lastname: Kim
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis; D018395:CA-19-9 Antigen / Q000032:analysis; D017322:Clinical Trials, Phase II as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods* / Q000706:statistics & numerical data; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D016016:Proportional Hazards Models; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D003841:Deoxycytidine; D000068258:Bevacizumab; D000093542:Gemcitabine