Unknown

Dataset Information

0

Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time.


ABSTRACT:

Purpose

Denosumab, an anti-RANK ligand monoclonal antibody, significantly increases bone metastasis-free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months.

Patients and methods

A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died.

Results

In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets.

Conclusion

Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression.

SUBMITTER: Smith MR 

PROVIDER: S-EPMC3795889 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time.

Smith Matthew R MR   Saad Fred F   Oudard Stephane S   Shore Neal N   Fizazi Karim K   Sieber Paul P   Tombal Bertrand B   Damiao Ronaldo R   Marx Gavin G   Miller Kurt K   Van Veldhuizen Peter P   Morote Juan J   Ye Zhishen Z   Dansey Roger R   Goessl Carsten C  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20130916 30


<h4>Purpose</h4>Denosumab, an anti-RANK ligand monoclonal antibody, significantly increases bone metastasis-free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMF  ...[more]

Similar Datasets

| S-EPMC8288034 | biostudies-literature
| S-EPMC3956942 | biostudies-other
| S-EPMC11222484 | biostudies-literature
| S-EPMC5617753 | biostudies-literature
| S-EPMC8816761 | biostudies-literature
| S-EPMC3671878 | biostudies-literature
| S-EPMC10529387 | biostudies-literature
| S-EPMC9338100 | biostudies-literature
| S-EPMC6390280 | biostudies-literature
| S-EPMC4289425 | biostudies-literature