Abstract 4422
Background
Men with PCa undergoing ADT experience bone loss that may be associated with fracture risk and reduced survival. Therapy with Dmab (Prolia®, Amgen, Inc) significantly increased bone mass and reduced vertebral fracture risk in men with nonmetastatic PCa receiving ADT. However, in that study (unlike other Dmab randomized trials), cataracts were reported more often in the Dmab group (4.7% vs 1.2% for placebo [PBO]). This trial (NCT00925600) assessed the effect of Dmab on LO (cataract) development or progression in men with nonmetastatic PCa receiving ADT.
Methods
Men aged ≥30 years with nonmetastatic PCa with bilateral orchiectomy or initiated ADT were randomized 1:1 to receive Dmab 60 mg or PBO subcutaneously every 6 months, stratified by Lens Opacities Classification System III (LOCS III) score (<3.0 at all sites, ≥3.0 at any site), age (<75, ≥75 years), and prior cataract history. The primary endpoint was LO development or progression by month 12 based on a change of ≥ 1.0 in posterior subcapsular cataract, ≥1.0 in cortical cataract, or ≥ 0.7 in nuclear opalescence per LOCS III score. Noninferiority was demonstrated if the upper bound of the 95% 2-sided CI was <10%.
Results
769 men with median age 71 were randomized to receive Dmab (n = 383) or PBO (n = 386). Baseline demographics were balanced. Development or progression of LO by month 12 was similar in the Dmab and PBO groups (33.5% vs 33.2%); the absolute risk difference was 0.4% (95% CI, –6.3 to 7.2; noninferiority P = 0.0026), indicating that Dmab was noninferior to PBO for the primary endpoint. Results for other LO endpoints also showed no increased risk of cataracts with Dmab (Table). Rates of AEs, serious AEs, AEs leading to treatment discontinuation, AEs of interest, and death were similar in the 2 groups.Table: 845P
| Endpoint (Parameters) | Dmab, n/N* (%) | PBO, n/N* (%) | Risk Difference (95% CI) |
|---|---|---|---|
| Development or progression of LO by month 12 | 127/379 (33.5) | 124/374 (33.2) | 0.4 (–6.3 to 7.2) Noninferiority P = 0.0026 |
| Incidence of LO development or progression by month 12 | 32/379 (8.4) | 40/374 (10.7) | –2.2 (–6.4 to 2.0) |
| Incidence of LO development or progression by month 6 | 72/379 (19.0) | 72/374 (19.3) | –0.3 (–5.9 to 5.3) |
| Incidence of confirmed LO development or progression by month 12† | 59/367 (16.1) | 66/361 (18.3) | –2.2 (–7.6 to 3.3) |
N is the number of patients with at least one post-baseline LOCS III measurement by month 12. †A confirmed LO development or progression was defined as two directly subsequent events per protocol assessments at the same location; for this endpoint, N is the number of patients with at least two post-baseline LOCS III measurements by month 12.
Conclusions
Dmab did not increase the short-term risk of cataracts in men with PCa.
Clinical trial identification
NCT00925600.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Editorial Acknowledgement
This study was funded by Amgen Inc. The authors also wish to acknowledge Rick Davis (Complete Healthcare Communications, LLC, West Chester, PA), whose work was funded by Amgen Inc., and Albert Rhee (Amgen Inc.,Thousand Oaks, CA) for assistance with the writing of this abstract.
Disclosure
S.T. Tagawa: Consulting fees, research grants (paid to Weill Cornell Medicine): Lilly, Sanofi, Janssen, Astellas, Progenics, Millennium, Amgen, BMS, Dendreon, Rexahn, Bayer, Genentech, Newlink, Inovio, AstraZeneca, Immunomedics, Novartis, Aveo, Boehringer Ingelheim, Merck, Abbvie, Endocyte, Pfizer, Exelixis, Clovis, and Karyopharm; Consulting fees: Astellas, Janssen, Bayer, Sanofi, Endocyte, Immunomedics, Karyopharm, Abbvie, Tolmar. T. Dai, D. Jandial: Employee, Stockholder: Amgen Inc.