Phase II Randomized Study of Figitumumab plus Docetaxel and Docetaxel Alone with Crossover for Metastatic Castration-Resistant Prostate Cancer

作者：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

来源：Clinical Cancer Research, 2014, 20(7): 1925-1934.

DOI：10.1158/1078-0432.CCR-13-1869

Purpose: Figitumumab is a human IgG(2) 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). %26lt;br%26gt;Experimental Design: Prostate-specific antigen (PSA) response was the primary endpoint; response assessment on the two arms was noncomparative and tested separately; H-0 = 0.45 versus HA = 0.60 (alpha = 0.05; beta = 0.09) for Arm A; H-0 = 0.05 versus H-A = 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. %26lt;br%26gt;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 treatmentrelated grade 3/4 adverse events (75% vs. 56%), particularly hyperglycemia, diarrhea, and asthenia, as well as treatmentrelated serious adverse events (41% vs. 15%), and allcausality grade 5 adverse events (18% vs. 8%). %26lt;br%26gt;Conclusion: IGF1R targeting may merit further evaluation in this disease in selected populations, but combination with docetaxel is not recommended.

• 出版日期2014-4-1
• 单位McGill; 河北医科大学