Phase II randomized study of figitumumab plus docetaxel and docetaxel alone with crossover for metastatic castration-resistant prostate cancer.

Abstract

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.

• Authors: Johann S de Bono, Josep M Piulats, Hardev S Pandha, Daniel P Petrylak, Fred Saad, Luis Miguel A Aparicio, Shahneen K Sandhu, Peter Fong, Silke Gillessen, Gary R Hudes, Tao Wang, Judith Scranton, Michael N Pollak
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 7 Pg. 1925-34 (04 01 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 24536060 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 AACR.

Chemical References

• Antibodies, Monoclonal
• Taxoids
• Docetaxel
• Receptor, IGF Type 1
• figitumumab

Topics

• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Docetaxel
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Prostatic Neoplasms, Castration-Resistant (drug therapy, pathology)
• Receptor, IGF Type 1 (immunology, therapeutic use)
• Taxoids (administration & dosage)