TY - JOUR
T1 - Phase III prospective randomized comparison trial of depot octreotide plus interferon Alfa-2b versus depot octreotide plus bevacizumab in patients with advanced carcinoid tumors
T2 - SWOG S0518
AU - Yao, James C.
AU - Moran, Cesar
AU - Guthrie, Katherine A.
AU - McDonough, Shannon
AU - Strosberg, Jonathan R.
AU - Kulke, Matthew H.
AU - Chan, Jennifer A.
AU - Loconte, Noelle
AU - McWilliams, Robert R.
AU - Wolin, Edward M.
AU - Wolin, Edward M.
AU - Mattar, Bassam
AU - Chen, Helen
AU - Blanke, Charles D.
AU - Hochster, Howard S.
N1 - Funding Information:
Supported by National Clinical Trials Network Grants No. CA180888, CA180819, CA180858, CA180830, CA180801, and CA180834; NCI Community Oncology Research Program Grants No. CA189808, CA189953, CA189822, CA189830, CA189954, CA189971, CA189856, CA189972, CA189858, CA189821, CA189829, CA189872, CA189952, CA139519, CA189854, CA189809, CA180799, CA180820, CA180821, and CA025224; legacy Grants No. CA35128, CA11083, CA76429, CA73590, CA68183, CA12644, CA37981, CA76462, CA16385, and CA04919 from the National Cancer Institute; and in part by Genentech.
Publisher Copyright:
Copyright © 2017 American Society of Clinical Oncology. All rights reserved.
PY - 2017/5/20
Y1 - 2017/5/20
N2 - Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-a-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-a-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-a-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.
AB - Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-a-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-a-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-a-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.
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U2 - 10.1200/JCO.2016.70.4072
DO - 10.1200/JCO.2016.70.4072
M3 - Article
C2 - 28384065
AN - SCOPUS:85022183540
SN - 0732-183X
VL - 35
SP - 1695
EP - 1703
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15
ER -