PURPOSE:R1507 is a selective, fully human, recombinant monoclonal antibody (immunoglobulin G1 subclass) against insulin-like growth factor-1 receptor (IGF-1R). The strong preclinical evidence supporting coinhibition of IGF-1R and epidermal growth factor receptor (EGFR) as anticancer therapy prompted this study. PATIENTS AND METHODS: Patients with advanced-stage non-small-cell lung cancer (NSCLC) with progression following one or two prior regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, and measurable disease were eligible. Patients were randomly assigned to receive erlotinib (150 mg orally once a day) in combination with either placebo, R1507 9 mg/kg weekly, or R1507 16 mg/kg intravenously once every 3 weeks. Treatment cycles were repeated every 3 weeks. The primary end point was comparison of the 12-week progression-free survival (PFS) rate. RESULTS: In all, 172 patients were enrolled: median age, 61 years; female, 33%; never-smokers, 12%; and performance status 0 or 1, 88%. The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm. Grades 3 to 4 adverse events occurred in 37%, 44%, and 48% of patients with placebo, R1507 weekly, and R1507 every 3 weeks, respectively. The 12-week PFS rates were 39%, 37%, and 44%, and the median overall survival was 8.1, 8.1, and 12.1 months for the three groups, respectively, with statistically nonsignificant hazard ratios. The 12-week PFS rate in patients with KRAS mutation was 36% with R1507 compared with 0% with placebo. CONCLUSION: The combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC. Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR.
RCT Entities:
PURPOSE: R1507 is a selective, fully human, recombinant monoclonal antibody (immunoglobulin G1 subclass) against insulin-like growth factor-1 receptor (IGF-1R). The strong preclinical evidence supporting coinhibition of IGF-1R and epidermal growth factor receptor (EGFR) as anticancer therapy prompted this study. PATIENTS AND METHODS: Patients with advanced-stage non-small-cell lung cancer (NSCLC) with progression following one or two prior regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, and measurable disease were eligible. Patients were randomly assigned to receive erlotinib (150 mg orally once a day) in combination with either placebo, R1507 9 mg/kg weekly, or R1507 16 mg/kg intravenously once every 3 weeks. Treatment cycles were repeated every 3 weeks. The primary end point was comparison of the 12-week progression-free survival (PFS) rate. RESULTS: In all, 172 patients were enrolled: median age, 61 years; female, 33%; never-smokers, 12%; and performance status 0 or 1, 88%. The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm. Grades 3 to 4 adverse events occurred in 37%, 44%, and 48% of patients with placebo, R1507 weekly, and R1507 every 3 weeks, respectively. The 12-week PFS rates were 39%, 37%, and 44%, and the median overall survival was 8.1, 8.1, and 12.1 months for the three groups, respectively, with statistically nonsignificant hazard ratios. The 12-week PFS rate in patients with KRAS mutation was 36% with R1507 compared with 0% with placebo. CONCLUSION: The combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC. Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Razelle Kurzrock; Amita Patnaik; Joseph Aisner; Terri Warren; Stephen Leong; Robert Benjamin; S Gail Eckhardt; Joseph E Eid; Gerard Greig; Kai Habben; Cinara D McCarthy; Lia Gore Journal: Clin Cancer Res Date: 2010-04-06 Impact factor: 12.531
Authors: H E Jones; L Goddard; J M W Gee; S Hiscox; M Rubini; D Barrow; J M Knowlden; S Williams; A E Wakeling; R I Nicholson Journal: Endocr Relat Cancer Date: 2004-12 Impact factor: 5.678
Authors: M Esteller; J Garcia-Foncillas; E Andion; S N Goodman; O F Hidalgo; V Vanaclocha; S B Baylin; J G Herman Journal: N Engl J Med Date: 2000-11-09 Impact factor: 91.245
Authors: W A Palmisano; K K Divine; G Saccomanno; F D Gilliland; S B Baylin; J G Herman; S A Belinsky Journal: Cancer Res Date: 2000-11-01 Impact factor: 12.701
Authors: Diane Lauren Reidy; Efsevia Vakiani; Marwan G Fakih; Muhammad Wasif Saif; Joel Randolph Hecht; Noah Goodman-Davis; Ellen Hollywood; Jinru Shia; Jonathan Schwartz; Kumari Chandrawansa; Aruna Dontabhaktuni; Hagop Youssoufian; David B Solit; Leonard B Saltz Journal: J Clin Oncol Date: 2010-08-16 Impact factor: 44.544
Authors: Floriana Morgillo; Woo-Young Kim; Edward S Kim; Fortunato Ciardiello; Waun Ki Hong; Ho-Young Lee Journal: Clin Cancer Res Date: 2007-05-01 Impact factor: 12.531
Authors: Daniel D Karp; Luis G Paz-Ares; Silvia Novello; Paul Haluska; Linda Garland; Felipe Cardenal; L Johnetta Blakely; Peter D Eisenberg; Corey J Langer; George Blumenschein; Faye M Johnson; Stephanie Green; Antonio Gualberto Journal: J Clin Oncol Date: 2009-04-20 Impact factor: 44.544
Authors: A Gualberto; M L Hixon; D D Karp; D Li; S Green; M Dolled-Filhart; L G Paz-Ares; S Novello; J Blakely; C J Langer; M N Pollak Journal: Br J Cancer Date: 2010-11-23 Impact factor: 7.640
Authors: Yixuan Gong; Evelyn Yao; Ronglai Shen; Aviva Goel; Maria Arcila; Julie Teruya-Feldstein; Maureen F Zakowski; Stanley Frankel; Martin Peifer; Roman K Thomas; Marc Ladanyi; William Pao Journal: PLoS One Date: 2009-10-06 Impact factor: 3.240
Authors: Collin M Blakely; Evangelos Pazarentzos; Victor Olivas; Saurabh Asthana; Jenny Jiacheng Yan; Irena Tan; Gorjan Hrustanovic; Elton Chan; Luping Lin; Dana S Neel; William Newton; Kathryn L Bobb; Timothy R Fouts; Jeffrey Meshulam; Matthew A Gubens; David M Jablons; Jeffrey R Johnson; Sourav Bandyopadhyay; Nevan J Krogan; Trever G Bivona Journal: Cell Rep Date: 2015-04-02 Impact factor: 9.423