title: A phase 2 trial of R1507, a monoclonal antibody to the insulin-like growth factor-1 receptor (IGF-1R), in patients with recurrent or refractory rhabdomyosarcoma, osteosarcoma, synovial sarcoma, and other soft tissue sarcomas: results of a Sarcoma Alliance for Research Through Collaboration study.
abstract: BACKGROUND
  Insulin-like growth factor-1 receptor (IGF-1R) is implicated in the pathogenesis of rhabdomyosarcoma (RMS), osteosarcoma (OS), and synovial sarcoma (SS). The authors conducted a multi-institutional phase 2 trial of the monoclonal antibody R1507 in patients with various subtypes of recurrent or refractory sarcomas.
  
  
  METHODS
  Eligibility criteria included age ≥ 2 years and a diagnosis of recurrent or refractory RMS, OS, SS, and other soft tissue sarcomas. Patients received a weekly dose of 9 mg/kg R1507 intravenously. The primary endpoint was the best objective response rate using World Health Organization criteria. Tumor imaging was performed every 6 weeks × 4 and every 12 weeks thereafter.
  
  
  RESULTS
  From December 2007 through August 2009, 163 eligible patients from 33 institutions were enrolled. The median patient age was 31 years (range, 7-85 years). Histologic diagnoses included OS (n = 38), RMS (n = 36), SS (n = 23), and other sarcomas (n = 66). The overall objective response rate was 2.5% (95% confidence interval, 0.7%-6.2%). Partial responses were observed in 4 patients, including 2 patients with OS, 1 patient with RMS, and 1 patient with alveolar soft part sarcoma. Four additional patients (3 with RMS and 1 with myxoid liposarcoma) had a ≥ 50% decrease in tumor size that lasted for <4 weeks. The median progression-free survival was 5.7 weeks, and the median overall survival was 11 months. The most common grade 3/4 toxicities were metabolic (12%), hematologic (6%), gastrointestinal (4%), and general constitutional symptoms (8%).
  
  
  CONCLUSIONS
  R1507 is safe and well tolerated but has limited activity in patients with recurrent or refractory bone and soft tissue sarcomas. Additional studies to help identify the predictive factors associated with clinical benefit in selected histologies such as RMS appear to be warranted.
authors.affiliation: Solid Tumor Division, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Pappo
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
authors.forename: John J
authors.initials: JJ
authors.lastname: Crowley
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bolejack
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: Rashmi
authors.initials: R
authors.lastname: Chugh
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Grippo
authors.forename: Georgina
authors.initials: G
authors.lastname: Dall
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Staddon
authors.forename: Sant P
authors.initials: SP
authors.lastname: Chawla
authors.forename: Robert G
authors.initials: RG
authors.lastname: Maki
authors.forename: Dejka M
authors.initials: DM
authors.lastname: Araujo
authors.forename: Birgit
authors.initials: B
authors.lastname: Geoerger
authors.forename: Kristen
authors.initials: K
authors.lastname: Ganjoo
authors.forename: Neyssa
authors.initials: N
authors.lastname: Marina
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Scott M
authors.initials: SM
authors.lastname: Schuetze
authors.forename: Warren A
authors.initials: WA
authors.lastname: Chow
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Helman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D006801:Humans; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000276:immunology*; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017526:Receptor, IGF Type 1; C551399:teprotumumab
keywords: IGF-1R; SARC; insulin-like growth factor; sarcoma