title: Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518.
abstract: Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs.
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: James C
authors.initials: JC
authors.lastname: Yao
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Guthrie
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Cesar
authors.initials: C
authors.lastname: Moran
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Strosberg
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Kulke
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Chan
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Noelle
authors.initials: N
authors.lastname: LoConte
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Robert R
authors.initials: RR
authors.lastname: McWilliams
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Wolin
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Bassam
authors.initials: B
authors.lastname: Mattar
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Shannon
authors.initials: S
authors.lastname: McDonough
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Helen
authors.initials: H
authors.lastname: Chen
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blanke
authors.affiliation: James C. Yao and Cesar Moran, MD Anderson Cancer Center, Houston, TX; Katherine A. Guthrie and Shannon McDonough, Fred Hutchinson Cancer Research Center, Seattle, WA; Jonathan R. Strosberg, H. Lee Moffitt Cancer Center, Tampa, FL; Matthew H. Kulke and Jennifer A. Chan, Dana Farber Cancer Institute, Boston, MA; Noelle LoConte, University of Wisconsin, Carbone Cancer Center, Madison, WI; Robert R. McWilliams, Mayo Clinic College of Medicine, Rochester, MN; Edward M. Wolin, University of Kentucky, Lexington, KY; Edward M. Wolin, Montifiore Einstein Cancer Center, New York, NY; Bassam Mattar, Wichita NCORP/Cancer Center of Kansas, Wichita, KS; Helen Chen, NCI Cancer Therapy Evaluation Program, Bethesda, MD; Charles D. Blanke, Oregon Health & Science University, Portland, OR; and Howard S. Hochster, Yale Cancer Center, New Haven, CT.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Hochster
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage; D002276:Carcinoid Tumor / Q000188:drug therapy*; D018572:Disease-Free Survival; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000068258:Bevacizumab; D015282:Octreotide