BERLIN—Men with non-metastatic prostate cancer who begin androgen deprivation therapy (ADT) with vertebral fractures at baseline have shorter survival time compared with those free of baseline fractures, according to an international study presented at the joint congress of the European Cancer Organization and European Society for Medical Oncology.
“This trend remained, even after adjusting for the risk factors of age and prior duration of ADT,” said Fred Saad, MD of the Centre Hospitalier de l’Université de Montréal in Canada, who presented the findings.
In patients treated with denosumab, researchers observed a reduced likelihood of new fractures and no difference in mortality, he reported.
Previous studies have shown that the four-year fracture risk is about 19% in prostate cancer patients receiving ADT compared with 13% among those not receiving ADT.
The study by Dr. Saad’s group, which was sponsored by Amgen, which makes denosumab, assessed the effect of the presence or absence of baseline prevalent vertebral fractures on overall survival at 36 months for all patients and according to treatment with denosumab (60 mg subcutaneously every six months for a total of six doses) versus placebo. Each study arm had 734 patients. The primary end point was the effect of denosumab on lumbar spine bone mineral density (BMD).
The mean age was 75 years, and median ADT duration at study entry was 20 months. Mean lumbar spine BMD T-score was -0.31 in the denosumab arm and -0.41 in the placebo arm. Mean total hip BMD T-score was -0.87 and -0.888, respectively. Prevalent vertebral fractures were diagnosed in 21% and 24%, respectively.
According to Dr. Saad, this is the first prospective study of the effect of baseline vertebral fractures on mortality.
The mortality at 36 months was 7.6% among patients with vertebral fractures at baseline compared with 5.1% for those without these fractures, a difference that translated into a 57% increased risk of vertebral fracture. In the placebo group, mortality was 9.2% for those with fractures at baseline versus 4.6% for those without fractures, a significant doubling of risk. In the denosumab arm, the proportions were 5.8% and 5.6%, respectively, a nonsignificant difference.
“The difference disappeared with denosumab,” he noted. He added that this decrease in mortality is perhaps related to protective effect, as denosumab was associated with a highly significant increase from baseline in BMD whereas the placebo arm lost BMD.
In addition, the proportion of patients who experienced new fractures was 3.3% in the placebo arm and 1% in the denosumab group at 24 months and 3.9% and 1.5%, respectively, at 36 months.
“These findings support the association of fracture with overall survival in men with nonmetastatic prostate cancer,” he said.