Results from a retrospective study show that the addition of bone resorption inhibitors (BRIs), including zoledronic acid and denosumab (Xgeva), to abiraterone plus prednisolone was associated with significantly longer overall survival (OS). The median OS was increased by nearly 9 months among recipients, compared with men who didn’t receive these drugs in this setting.
The findings were published online July 22, 2021, in JAMA Network Open.
All men with prostate cancer should receive BRIs “as the disease reaches the castration resistance with bone metastases stage, as recommended by the international guidelines,” lead author Edoardo Francini, MD, PhD, of the University of Florence (Italy) said in a comment.
While there is no evidence that BRIs – when used alone – may improve survival in metastatic castration-resistant prostate cancer (mCRPC) with bone involvement, there has been a “suggestion” of a survival benefit with BRIs when combined with other anticancer therapies in this setting, say the authors.
So Dr. Francini and a team of international coinvestigators looked at the medical records of men with mCRPC and bone metastases treated at eight institutions in Canada, Europe, and the United States and focused on patients who received abiraterone acetate (with prednisone) because it is the most common first-line therapy in this setting.
Patients were classified by receipt versus nonreceipt of concomitant BRIs and subclassified by volume of disease (high or low volume).
There were two cohorts in the study population: 529 men (71.0%) who received abiraterone alone and 216 men (29.0%) who received abiraterone plus BRIs. The median follow-up was 23.5 months.
Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone alone cohort (31.8 vs. 23.0 months; hazard ratio, 0.65; P < .001).
Notably, the OS benefit in the BRI cohort was greater for patients with high-volume versus low-volume disease (33.6 vs. 19.7 months; HR, 0.51; P < .001).
Dr. Francini hopes the new study results can effect change. “Hopefully, clinicians will be more inclined to use bone resorption inhibitors in combination with abiraterone acetate plus prednisone as soon as the disease reaches the castration-resistance with bone metastases stage, as recommended by the international guidelines.”
Importance of bone-targeted drugs
“This study highlights the importance of bone-targeted therapy in current practice for men with mCRPC and bone metastases,” Samuel Takvorian, MD, and Naomi Haas, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.
But the study also reveals that work needs to be done to get clinicians to prescribe BRIs, they said, and that clinical pathways and behavioral “nudges” could help promote adoption.
Most (71%) of the men in this study did not get bone protective drug therapy, they pointed out, even though they were being treated at major hospital systems.
So, why aren’t more men receiving BRIs?
“I think this is less likely due to poor communication from professional societies (the guidelines are clear) and more likely due to bone health being low on the list of priorities for these patients and clinician uncertainty and/or lack of appreciation of the clinical benefit of these agents,” Dr. Takvorian said in an interview.
“When prostate cancer progresses to the castration-resistant phase, clinicians (and patients) rightfully are focused on the next cancer-directed therapy. However, this may be at the expense of supportive care, like bone agents, which often gets short shrift,” he added.
As would be expected, the men who were taking BRIs had a significantly shorter time to first skeletal-related events (SREs), compared with those who were not (32.4 vs. 42.7 months; HR, 1.27; P = .04), and the risk of a first SRE was more than double in the subgroup with low-volume disease (HR, 2.29; P < .001).
“These SREs collectively represent a clinically meaningful outcome that is often measured in clinical trials,” the editorialists observed. In the current study, SREs were comprised of pathological fractures, spinal cord compression, or the need for surgery or radiotherapy to bone.
“Up to one-half of men with mCRPC, the advanced and often fatal stage of disease, experience SREs, which are associated with considerable morbidity, decreased survival, and increased health care utilization and costs,” they wrote.
