NO SURVIVAL BENEFIT OF ADJUVANT DENOSUMAB IN PROSTATE CANCER

In a recently reported phase III trial, denosumab (Xgeva) significantly increased bone metastasis–free survival and delayed time to first bone metastasis but did not improve overall survival compared with placebo in men with nonmetastatic castration-resistant prostate cancer and baseline prostate specific antigen (PSA) ≥ 8.0 ng/mL or PSA doubling time ≤ 10.0 months. In an exploratory analysis reported in Journal of Clinical Oncology, Matthew R. Smith, MD, PhD, of Massachusetts General Hospital Cancer Center, and colleagues investigated the relationship between PSA doubling time and bone metastasis–free survival in denosumab and placebo recipients. Denosumab consistently increased bone metastasis–free survival according to decreasing PSA doubling time. No improvements in overall survival were observed with denosumab according to PSA doubling time.

The study involved 1,432 men with nonmetastatic castration-resistant prostate cancer randomly assigned to receive monthly subcutaneous denosumab 120 mg (n = 716) or placebo (n = 716). Bone metastasis–free survival was analyzed according to PSA doubling times of ≥ 10, ≤ 6, and ≤ 4 months.

Increased Bone Metastasis–Free Survival

Denosumab treatment was associated with median bone metastasis–free survival increases of 6.0 months (28.4 vs 22.4 months, hazard ratio [HR] = 0.84, P = .042) in patients with PSA doubling time ≤ 10 months (n = 1,154), 7.2 months (25.9 vs 18.7 months, HR = 0.77, P = .006) in those with doubling time ≤ 6 months (n = 846), and 7.5 months (HR = 0.71, P = .004) in those with doubling time ≤ 4 months (n = 552). Median time to first bone metastasis was significantly reduced with denosumab in patients with PSA doubling time ≤ 6 months (26.5 vs 22.1 months, HR = 0.80, P = .026) and ≤ 4 months (26.4 vs 18.5 months, HR = 0.71, P = .008).

No Overall Survival Differences

No differences in overall survival were observed between the denosumab and placebo groups according to PSA doubling time of ≤ 10 months (HR = 1.00, P = .960), ≤ 6 months (HR = 0.99, P = .895), or ≤ 4 months (HR = 0.97, P = .829). No differences in time to prostate cancer progression were observed according to doubling time of ≤ 10 months (HR = 0.90, P = .179), ≤ 6 months (HR = 0.87, P= .110), or ≤ 4 months (HR = 0.82, P = .073).

The investigators concluded: “Patients with shorter PSA doubling time are at greater risk for bone metastasis or death. Denosumab consistently improves [bone metastasis–free survival] in men with shorter PSA doubling time and seems to have the greatest treatment effects in men at high risk for progression.”

The study was supported by Amgen and others.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.