Prolonged Response to an IGF-1 Receptor Antibody in a Patient with Metastatic Castration Prostate Cancer with Neuroendocrine Differentiation

The androgen receptor is the main therapeutic target that has been successfully exploited through direct inhibition to extend survival of patients with metastatic castration-resistant prostate cancer (mCRPC). We present a patient who participated in a Phase II study of an antagonist antibody to insulin-like growth factor 1 receptor (IGF-1R) in men with mCRPC and experienced over five years of stable disease. His disease was rapidly progressing before exposure to the antibody and resumed its aggressive behavior following discontinuation of therapy, strongly supporting the attribution of his stable disease to IGF-1R inhibition. His pre-treatment biopsy exhibited increased protein expression of IGF-1R (and its downstream effector, phosphorylated-S6). Consequently, agents that target IGF-1R may provide profound and durable responses in a subset of patients and upfront molecular selection may enable us to identify those most likely to benefit.