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.


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%).


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.

Document Type


Publication Date


Notes/Citation Information

Published in Journal of Clinical Oncology, v. 35, no. 15, p. 1695-1703.

© 2017 by American Society of Clinical Oncology

The copyright holder has granted the permission for posting the article here.

Digital Object Identifier (DOI)


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.

Related Content

Clinical trial information: NCT00569127

Supplements: https://doi.org/10.1200/JCO.2016.70.4072

Disclosures provided by the authors are available with this article at jco.org.

protocol_2016.704072.pdf (725 kB)
Study Protocol