PURPOSE: Figitumumab is a human IgG2 monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF-1R), with antitumor activity in prostate cancer.
This phase II trial randomized chemotherapy-naïve men with progressing castration-resistant prostate cancer to receive figitumumab every 3 weeks with docetaxel/prednisone (Arm A) or docetaxel/prednisone alone (Arm B1). At progression on Arm B1, patients could cross over to the combination (Arm B2).
EXPERIMENTAL DESIGN: Prostate-specific antigen (PSA) response was the primary endpoint; response assessment on the two arms was noncomparative and tested separately; H0 = 0.45 versus HA = 0.60 (α = 0.05; β = 0.09) for Arm A; H0 = 0.05 versus HA = 0.20 (α = 0.05, β = 0.10) for Arm B2. A comparison of progression-free survival (PFS) on Arms A and B1 was planned.
RESULTS: A total of 204 patients were randomized and 199 treated (Arm A: 97; Arm B1: 102); 37 patients crossed over to Arm B2 (median number of cycles started: Arm A = 8; B1 = 8; B2 = 4). PSA responses occurred in 52% and 60% of Arms A and B1, respectively; the primary PSA response objective in Arm A was not met. Median PFS was 4.9 and 7.9 months, respectively (HR = 1.44; 95% confidence interval, 1.06-1.96). PSA response rate was 28% in Arm B2. The figitumumab combination appeared more toxic, with more treatment-related grade 3/4 adverse events (75% vs. 56%), particularly hyperglycemia, diarrhea, and asthenia, as well as treatment-related serious adverse events (41% vs. 15%), and all-causality grade 5 adverse events (18% vs. 8%).
CONCLUSION: IGF-1R targeting may merit further evaluation in this disease in selected populations, but combination with docetaxel is not recommended.
Written by:
de Bono JS, Piulats JM, Pandha HS, Petrylak DP, Saad F, Aparicio LM, Sandhu SK, Fong P, Gillessen S, Hudes GR, Wang T, Scranton J, Pollak MN. Are you the author?
Royal Marsden NHS Foundation Trust and The Institute of Cancer Research UK, Sutton; Institut Català d'Oncologia, L'Hospitalet, Barcelona; University of Surrey, Surrey, United Kingdom; Yale University Cancer Center, New Haven; Centre Hospitalier de l'Universite de Montreal, Montreal; A Coruña University Hospital, A Coruña, Spain; Kantonsspital St. Gallen, St. Gallen, Switzerland; Fox Chase Cancer Center, Philadelphia, Pennsylvania; Pfizer Inc, Groton, Connecticut; and Lady Davis Institute for Medical Research, Jewish General Hospital and McGill University, Montreal, Quebec, Canada.
Reference: Clin Cancer Res. 2014 Mar 13. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-13-1869
PubMed Abstract
PMID: 24536060
UroToday.com mCRPC Treatment Section
