Bone-Modifying Agents in Patients With High-Risk Metastatic Castration-Sensitive Prostate Cancer Treated With Abiraterone Acetate - PubMed (original) (raw)

Clinical Trial

Bone-Modifying Agents in Patients With High-Risk Metastatic Castration-Sensitive Prostate Cancer Treated With Abiraterone Acetate

Wataru Fukuokaya et al. JAMA Netw Open. 2024.

Abstract

Importance: The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with abiraterone acetate plus prednisone (AAP) remains unclear.

Objective: To investigate the association between BMA use and the outcomes of patients with mCSPC receiving AAP.

Design, setting, and participants: In this cohort study, a post hoc analysis of individual participant data from the LATITUDE trial was performed. The LATITUDE trial, a phase 3 randomized clinical trial, aimed to assess the efficacy of AAP and androgen deprivation therapy (ADT) vs dual-placebo and ADT in patients with high-risk mCSPC (data cutoff, August 15, 2018). Eligible patients had newly diagnosed prostate cancer with metastases and at least 2 of 3 high-risk factors (Gleason score ≥8, presence of ≥3 lesions on bone scan, or presence of measurable visceral metastasis). The trial was conducted at 235 sites in 34 countries. Data for the present study were evaluated from July 18 to September 23, 2023.

Exposures: Use of BMAs was defined as the administration of bisphosphonates and denosumab within 90 days before and after randomization.

Main outcomes and measures: The primary outcomes were time to skeletal-related events (SREs) and overall survival (OS). An SRE was defined as a clinical or pathological fracture, spinal cord compression, palliative radiation to bone, or surgery involving bone. Differences in these outcomes were examined using the restricted mean survival time from inverse probability of treatment weighting-adjusted Kaplan-Meier curves, estimated until the last event was observed (longest time observed, 63.9 months). Treatment × covariate interactions were analyzed using weighted Cox proportional hazards regression models for the total cohort.

Results: In the total cohort of 1199 patients (956 [79.7%] younger than 75 years), 597 (49.8%) received AAP and ADT, including 474 (79.4%) younger than 75 years and 384 (64.3%) with more than 10 bone metastases (AAP cohort); 602 (50.2%) were treated with dual placebo and ADT, including 482 (80.1%) younger than 75 years and 377 (62.6%) with more than 10 bone metastases (ADT cohort). In the AAP cohort, 132 patients (22.1%) received BMAs, while in the ADT cohort, 131 (21.8%) did. Zoledronic acid was the most frequently administered BMA in both the AAP (93 [70.5%]) and the ADT (88 [67.2%]) cohorts. During the median follow-up of 51.8 (IQR, 47.2-57.0) months in the AAP cohort, BMA use was associated with a longer time to SRE (difference, 7.8 [95% CI, 4.2-11.3] months) but not with OS (difference, 1.6 [95% CI, -2.5 to 5.8] months). In the ADT cohort, BMA use was associated with both time to SRE (difference, 9.3 [95% CI, 5.2-13.3] months) and OS (difference, 5.5 [95% CI, 3.2-9.8] months). No evidence was found that the outcomes of BMA varied by AAP or ADT (hazard ratio for time to SRE, 0.99 [95% CI, 0.48-2.08]; P = .99 for interaction; hazard ratio for OS, 1.31 [95% CI, 0.88-1.96]; P = .18 for interaction).

Conclusions and relevance: The findings of this cohort study suggest that use of BMAs was associated with a longer time to SRE in patients with high-risk mCSPC treated with ADT, with or without AAP, suggesting that BMA use might provide benefits to this population.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Fukuokaya reported receiving grants-in-aid for scientific research from Japan Society for the Promotion of Science outside the submitted work. Dr Igarashi reported nonfinancial support from Jikei University Hospital during the conduct of the study and personal fees from the University of Pittsburgh outside the submitted work. Dr Kimura reported consulting for Astellas Pharma, Bayer AG, Janssen Pharmaceuticals, and Sanofi SA. No other disclosures were reported.

Figures

Figure 1.. Crude and Inverse Probability of Treatment Weighting (IPTW)–Adjusted Kaplan-Meier Curves Based on Bone-Modifying Agent (BMA) Use in the Abiraterone Acetate Plus Prednisone Cohort

Shaded areas indicate 95% CIs. OS indicates overall survival; SRE, skeletal-related event.

Figure 2.. Differences in Restricted Mean Survival Times Between Bone-Modifying Agent Users and Nonusers in the Abiraterone Acetate Plus Prednisone Cohort

Differences were calculated as restricted mean survival time for body-modifying agent users – restricted mean survival time for nonusers. A difference greater than 0 indicates longer survival in users, whereas a difference less than 0 indicates longer survival in nonusers. Shaded areas indicate 95% CIs.

Figure 3.. Crude and Inverse Probability of Treatment Weighting (IPTW)–Adjusted Kaplan-Meier Curves Based on Bone-Modifying Agent (BMA) Use in the Androgen Deprivation Therapy Cohort

Shaded areas indicate 95% CIs. OS indicates overall survival; SRE, skeletal-related event.

Figure 4.. Differences in Restricted Mean Survival Times Between Bone-Modifying Agent Users and Nonusers in the Androgen Deprivation Therapy Cohort

References

1. Surveillance, Epidemiology, and End Results Program . Cancer stat facts: prostate cancer. Accessed September 24, 2023. https://seer.cancer.gov/statfacts/html/prost.html
1. Baek YH, Jeon HL, Oh IS, Yang H, Park J, Shin JY. Incidence of skeletal-related events in patients with breast or prostate cancer-induced bone metastasis or multiple myeloma: a 12-year longitudinal nationwide healthcare database study. Cancer Epidemiol. 2019;61:104-110. doi:10.1016/j.canep.2019.05.013 - DOI - PubMed
1. Saad F, Gleason DM, Murray R, et al. ; Zoledronic Acid Prostate Cancer Study Group . A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002;94(19):1458-1468. doi:10.1093/jnci/94.19.1458 - DOI - PubMed
1. Fizazi K, Carducci M, Smith M, et al. . Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768):813-822. doi:10.1016/S0140-6736(10)62344-6 - DOI - PMC - PubMed
1. European Association of Urology . Prostate cancer. 2023. Accessed September 24, 2023. https://uroweb.org/guidelines/prostate-cancer

Bone-Modifying Agents in Patients With High-Risk Metastatic Castration-Sensitive Prostate Cancer Treated With Abiraterone Acetate - PubMed (original) (raw)