Association of Concomitant Bone Resorption Inhibitors With Overall Survival Among Patients With Metastatic Castration-Resistant Prostate Cancer and Bone Metastases Receiving Abiraterone Acetate With Prednisone as First-Line Therapy
Authors: Edoardo Francini, Francesco Montagnani, Pier Vitale Nuzzo, Miguel Gonzalez-Velez, Nimira S. Alimohamed, Pietro Rosellini, Irene Moreno-Candilejo, Antonio Cigliola, Jaime Rubio-Perez, Francesca Crivelli, Grace K. Shaw, Li Zhang, Roberto Petrioli, Carmelo Bengala, Guido Francini, Jesus Garcia-Foncillas, Christopher J. Sweeney, Celestia S. Higano, Alan H. Bryce, Lauren C. Harshman, Richard Lee-Ying, Daniel Y. C. Heng
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Bone resorption inhibitors (BRIs) are recommended by international guidelines to prevent skeletal-related events (SREs) among patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. Abiraterone acetate with prednisone is currently the most common first-line therapy for the treatment of patients with mCRPC; however, the clinical impact of the addition of BRIs to abiraterone acetate with prednisone in this disease setting is unknown. <h3>Objective</h3> To evaluate the association of the use of concomitant BRIs with overall survival (OS) and time to first SRE among patients with mCRPC and bone metastases receiving abiraterone acetate with prednisone as first-line therapy. <h3>Design, Setting, and Participants</h3> This retrospective cohort study collected data from 745 consecutive patients who began receiving abiraterone acetate with prednisone as first-line therapy for mCRPC with bone metastases between January 1, 2013, and December 31, 2016. Data were collected from 8 hospitals in Canada, Europe, and the US from June 15 to September 15, 2019. <h3>Exposures</h3> Patients were classified by receipt vs nonreceipt of concomitant BRIs and subclassified by volume of disease (high volume or low volume, using definitions from the Chemohormonal Therapy Vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer [CHAARTED] E3805 study) at the initiation of abiraterone acetate with prednisone therapy. <h3>Main Outcomes and Measures</h3> The primary end point was OS. The secondary end point was time to first SRE. The Kaplan-Meier method and Cox proportional hazards models were used. <h3>Results</h3> Of the 745 men (median age, 77.6 years [interquartile range, 68.1-83.6 years]; 699 White individuals [93.8%]) included in the analysis, 529 men (71.0%) received abiraterone acetate with prednisone alone (abiraterone acetate cohort), and 216 men (29.0%) received abiraterone acetate with prednisone plus BRIs (BRI cohort). A total of 420 men (56.4%) had high-volume disease, and 276 men (37.0%) had low-volume disease. The median follow-up was 23.5 months (95% CI, 19.8-24.9 months). Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone acetate cohort (31.8 vs 23.0 months; hazard ratio [HR], 0.65; 95% CI, 0.54-0.79;<i>P</i> &lt; .001). The OS benefit in the BRI cohort was greater for patients with high-volume vs low-volume disease (33.6 vs 19.7 months; HR, 0.51; 95% CI, 0.38-0.68;<i>P</i> &lt; .001). The BRI cohort also had a significantly shorter time to first SRE compared with the abiraterone acetate cohort (32.4 vs 42.7 months; HR, 1.27; 95% CI, 1.00-1.60;<i>P</i> = .04), and the risk of a first SRE was more than double in the subgroup with low-volume disease (HR, 2.29; 95% CI, 1.57-3.35;<i>P</i> &lt; .001). In the multivariable analysis, concomitant BRIs use was independently associated with longer OS (HR, 0.64; 95% CI, 0.52-0.79;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> In this study, the addition of BRIs to abiraterone acetate with prednisone as first-line therapy for the treatment of patients with mCRPC and bone metastases was associated with longer OS, particularly in patients with high-volume disease. These results suggest that the use of BRIs in combination with abiraterone acetate with prednisone as first-line therapy for the treatment of mCRPC with bone metastases could be beneficial.