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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
Phase II randomized study of figitumumab plus docetaxel and docetaxel alone with crossover for metastatic castration-resistant prostate cancer
Clin Cancer Res. 2014 Apr 1;20(7) :1925-34
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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-naive 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 (alpha = 0.05; beta = 0.09) for Arm A; H0 = 0.05 versus HA = 0.20 (alpha = 0.05, beta = 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.
de Bono, Johann S Piulats, Josep M Pandha, Hardev S Petrylak, Daniel P Saad, Fred Aparicio, Luis Miguel A Sandhu, Shahneen K Fong, Peter Gillessen, Silke Hudes, Gary R Wang, Tao Scranton, Judith Pollak, Michael N eng Clinical Trial, Phase II Randomized Controlled Trial Research Support, Non-U.S. Gov't Clin Cancer Res. 2014 Apr 1;20(7):1925-34. doi: 10.1158/1078-0432.CCR-13-1869. Epub 2014 Feb 17.