medwireNews: The addition of bone resorption inhibitors (BRIs) to abiraterone acetate plus prednisone is associated with improved survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases, especially if they have high-volume disease, researchers report.
“This survival association is consistent with the increasing body of evidence suggesting that treatment with concurrent BRIs may provide an additive benefit to life-prolonging agents approved for the treatment of mCRPC,” say Edoardo Francini (University of Florence, Italy) and team.
The retrospective cohort study reported in JAMA Network Open included 745 men from eight hospitals across Europe, Canada, and the USA who received first-line treatment for mCRPC with bone metastases between 2013 and 2016.
After a median follow-up of 23.5 months, the median overall survival (OS) was 31.8 months for the 216 patients who received abiraterone and prednisone with denosumab (61.1%) or zoledronic acid (38.9%) and 23.0 months for the 529 patients who received just abiraterone and prednisone. This equated to a significant hazard ratio (HR) for death of 0.64 in favor of BRI use after adjusting for a raft of clinicopathologic factors.
Among the 56% of patients with high-volume disease, defined as the presence of visceral disease and/or at least four bone metastases with one or more being outside the axis and pelvis, the median OS was significantly longer in those who did versus did not receive BRIs, at 33.6 and 19.7 months, respectively, and the risk for death was almost halved (HR=0.51).
By contrast, the 37% of participants who had low-volume disease did not derive a significant OS benefit from BRIs, at a median of 31.8 and 33.0 months in the BRI and no BRI arms respectively.
The researchers also found that patients taking a BRI had a significantly shorter median time to first skeletal-related event (SRE) than those who were not, at 32.4 versus 42.7 months (HR=1.27) in the overall study population.
This was also the case in men with low-volume disease, with a significant HR for first SRE of 2.29 for those who did versus did not receive a BRI. But there was only a trend toward a longer time to first SRE with BRIs in participants with high-volume disease, at an HR of 0.70.
The study authors note, however, that “there is currently no clear biological rationale that may explain the deleterious consequences of the addition of BRIs to abiraterone acetate with prednisone therapy for time to first SRE among men with low-volume disease, and these findings should be interpreted with caution.”
The authors of an accompanying commentary – Samuel Takvorian and Naomi Haas both from the University of Pennsylvania in Philadelphia, USA – say that “this study supports the hypothesis that BRIs may be particularly important for men with high-volume metastases, a hypothesis that warrants prospective testing in future studies.”
They point out that “[i]n a study population encompassing men with mCRPC and bone metastases for whom bone-targeted therapy is endorsed by international guidelines,” over 70% of participants were not given a BRI.
The commentators therefore emphasize that there is a “need for implementation work (such as clinical pathways and behavioral nudges to promote adoption) to bring evidence-based therapies to the patients who need them.”
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JAMA Netw Open 2021; 4: e2116536
JAMA Netw Open 2021; 4: e2117159