Denosumab versus zoledronic acid: analgesic and survival impact of an extended treatment regimen beyond 2 years in breast cancer

Background: Zoledronic acid (ZA) and denosumab (Dmab) are the standard of care for bone metastases, but there is no consensus on their long-term use. This study was conducted to evaluate treatment patterns (persistence, compliance, modification, and reintroduction of drug therapy), analgesic efficacy, clinical outcomes, and survival in patients with bone metastases from breast cancer treated beyond 24 months. Methods: In this retrospective observational study, patients who had received at least 24 months of regular q3-4w therapy with ZA or Dmab were analyzed for an additional two years. The primary outcomes were the analgesic effect, evaluated in terms of week average pain intensity (WAPI)), analgesic drug use (Word Health Organization analgesic scale WHO), and daily opioid doses (oral morphine equivalent, OMED) assessed at 3, 6, 12, 18, and 24 months, analyzed by Bayesian longitudinal mixed-effects models. Secondary outcomes included overall survival(OS) and adverse events. OS was analyzed using Kaplan-Meier curves, complemented by multivariable Cox models. Results: Among 355 patients analyzed, Dmab provided significantly superior pain relief compared with ZA, demonstrated by lower WAPI scores, reduced analgesic WHO escalation (OR: 0.07, 95 % CI 0.02-0.30), and lower opioid requirements (median OMED: 25 mg vs 67.3 mg). Incidence rates of SREs were similar between treatments. Dmab therapy improved OS (median: 35.8 vs. 29.9 months). Conclusions: These findings highlight the importance for clinicians to carefully consider these differences when selecting bone-modifying agents for patients with cancer-induced bone pain. Prospective studies are needed to confirm the survival benefit of Dmab.