Prostate cancer treatments, particularly hormone therapy (ADT) can have a significant effect on speeding up the process of thinning and weakening the bones. There are some available treatments (Zoledronic acid aka Zoladex and denosumab aka Xgeva) which are designed to slow down or reverse this process; however, they are known to have many adverse side effects themselves. These side effects can include severe fractures of the femur which could limit survival and cataracts. For this reason, these treatments are usually used later, when men become castrate resistant and metastatic.

According to results from a phase III trial that was presented at the 2018 ESMO Congress, contrary to previous data, denosumab was shown to decrease the risk of developing fractures without a higher incidence of cataracts in men with non-metastatic prostate cancer.

In a previous study, low-dose denosumab significantly increased bone mass and reduced vertebral fracture risk. However, unlike other randomized trials that evaluated denosumab, this study showed that this drug resulted in increased development of cataracts in those who received it compared with those who were given a placebo, said Scott T. Tagawa, MD, MS.

Tagawa said, “We wanted to prove if these [earlier] results were real and not just a fluke, so we undertook this newer study.”

In the randomized phase III trial (NCT00925600), men with non-metastatic prostate cancer with bilateral orchiectomy or initiated ADT were randomized 1:1 to receive 60 mg of denosumab every six months or placebo. They found that after 12 months the development or progression of cataracts was similar in the denosumab and placebo arms. They also found that the rates of adverse events leading to treatment discontinuation, and death were similar in the two arms.

Tagawa, ST, Dai, T, Jandial, D. Phase 3 double-blind study evaluating lens opacifications (LO) in patients with nonmetastatic prostate cancer (PCa) receiving denosumab for bone loss due to androgen deprivation therapy (ADT). Ann Oncol. 2018;29 (suppl): 8. doi: 10.1093/annonc/mdy284.