Abituzumab Improves Bone Lesion Progression, not PFS in CRPC

Abituzumab did not extend progression-free survival (PFS) compared with placebo in a phase II study of patients with metastatic castration-resistant prostate cancer. The agent did, however, offer a lower incidence of bone lesion progression, and researchers say it still warrants further investigation.

Previous research has suggested that integrins play a role in the progression of metastatic prostate cancer and associated bone lesions, wrote researchers led by Maha Hussain, MB, ChB, of the University of Michigan in Ann Arbor. Abituzumab is a pan-αv integrin inhibitor; a phase I trial previously showed that the agent has activity in patients with castration-resistant prostate cancer and bone metastases.

The new phase II trial randomized 180 patients between three arms: a 750-mg abituzumab group, a 1,500-mg abituzumab group, or placebo. All groups also received standard of care. The results were published in Clinical Cancer Research.

The primary endpoint of PFS was not improved with the study drug. The 750-mg group had a median PFS of 3.4 months, compared with 3.3 months with placebo, for a hazard ratio (HR) of 0.89 (95% CI, 0.57–1.39). The median PFS was 4.3 months with the higher abituzumab dose, though this still did not significantly differ from placebo, with an HR of 0.81 (95% CI, 0.52–1.26). Fewer than 25% of patients had died at the time of data cutoff, and overall survival data were thus not yet available.

There was an effect, however, on bone lesion progression. The cumulative incidence of bone lesion progression at 6 months was 23.6% for abituzumab patients, compared with 41.1% in placebo patients. At 12 months, the rates were 26.1% and 45.4%, respectively.

Grade 3 or higher treatment-emergent adverse events (TEAEs) were more common in the 1,500-mg abituzumab group, at 43.3% compared with 29.3% in the 750-mg group and 25.0% in the placebo group. Serious TEAEs, however, were similar, at 23.3%, 22.4%, and 26.7%, respectively. TEAEs leading to treatment discontinuation occurred in 13.3% of patients in the 1,500-mg group, 19.0% of patients in the 750-mg group, and 8.3% of placebo patients.

The authors concluded that the agent did not demonstrate the expected level of activity in these patients. “However, the data suggest that abituzumab has specific effects against prostate cancer–associated bone lesions, and there is a biological rationale for these effects,” they wrote. “As the management of bone lesions in patients with prostate cancer represents a specific therapeutic challenge and unmet need, our observations warrant further investigation.”