Differential Effect on Bone Lesions of Targeting Integrins: Randomized Phase II Trial of Abituzumab in Patients with Metastatic Castration-Resistant Prostate Cancer

Purpose: Integrins play a critical role in the progression of prostate cancer and its bone metastases. We investigated the use of the pan-alpha v integrin inhibitor abituzumab in chemotherapy-naive patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer. Experimental Design: PERSEUS (NCT01360840) was a randomized, double-blind phase II study. Men with pathologically confirmed prostate cancer and radiologic progression of bone lesions in the 28 days prior to randomization were assigned to receive abituzumab 750 mg or 1,500 mg or placebo (1: 1: 1) every 3 weeks in combination with luteinizing hormone-releasing hormone agonist/antagonist therapy. The primary endpoint was progression-free survival (PFS). Results: The intent-to-treat population comprised 180 patients, 60 in each arm. The primary endpoint of PFS was not significantly different with abituzumab-based therapy compared with placebo [abituzumab 750 mg, 3.4 months, HR = 0.89; 95% confidence interval (CI), 0.57-1.39; abituzumab 1,500 mg, 4.3 months, HR = 0.81; 95% CI, 0.52-1.26; placebo, 3.3 months], but the cumulative incidence of bone lesion progression was lower with abituzumab than with placebo for up to 24 months (cumulative incidence 23.6% vs. 41.1% at 6 months, 26.1% vs. 45.4% at 12 months). Two partial tumor responses were observed (1 abituzumab 1,500 mg and 1 placebo). Approximately 85% to 90% of patients experienced at least one treatment-emergent adverse event (TEAE) in the different arms, but the incidences of serious TEAEs and TEAEs with fatal outcome were similar in the three arms. Conclusions: Although PFS was not significantly extended, abituzumab appears to have specific activity in prostate cancer-associated bone lesions that warrants further investigation. (C) 2016 AACR.