1480P - Long term therapy with denosumab and zoledronic acid: A comparative real-world retrospective observational study on skeletal-related events and pain in patients with metastatic breast cancer

Background

Bone metastases (BM) due to breast cancer are associated with a high risk of pain and skeletal related events (SREs= pathological fractures, spinal cord compression, hypercalcemia). Treatment of BM includes radiotherapy (RT), bone surgery (BS), anticancer and antiresorptive drugs. The aim of the study was to compare zoledronic acid (ZA) and denosumab (Dmab) in reducing first SRE and bone pain in breast cancer patients with BM.

Methods

This monocentric retrospective study included breast cancer patients with bone metastases that received at least 24 infusions of ZA or Dmab, between January 2008 and January 2023. The endpoints were: occurrence of a SREs or RT/BS need, change in anticancer therapy, week average pain intensity, level of analgesic drug used (according to the WHO three-step analgesic ladder) and the opioid dose (using oral morphine equivalent mg, OME). These endpoints were evaluated during ZA or Dmab therapy. To evaluate the analgesic effect, three Bayesian longitudinal mixed effects models were implemented having as response variable the WHO ladder drug level, the pain intensity, and the OME. All models shared the same covariates and multiple regression models were used to study the associations.

Results

The study enrolled 364 patients (194 ZA and 170 Dmab). Dmab and ZA had a comparable effect on first SRE occurrence and on RT/BS referral incidence. The cumulative incidence of the first SRE was equal to 28.9% (24.2%-33.7%). At 1 and 2 years the cumulative incidence for the first SRE and the need of RT/BS was similar for AZ and Dmab (p=0.6, p> 0.9 respectively). In the three models Dmab had a significant analgesic effect respect to ZA: patients on Dmab were 89% less likely to increase one step on the WHO ladder. They also showed a reduction on average of 0.4 points (-0.67, -0.12, 95% CI) on the numerical rating scale. Finally, patients on Dmab took an average 0.77 mg OME dose (0.22-2.94, 95% CI) compared with 6.24 mg OME dose (3.6- 18, 95% CI) of ZA patients.

Conclusions

Dmab had a greater impact on preventing and reducing bone pain in breast cancer patients rather than ZA. However, long term AZ and Dmab were similar in preventing the first SRE and RT/BS need.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale dei tumori.

Funding

Has not received any funding.

Disclosure

E. Zecca: Other, Institutional, Invited Speaker: Amgen. A.T. Caraceni: Other, Institutional, Invited Speaker: Angelini, Shionogi, Kyowa Kirin, Molteni, Pfizer, Eli Lilly. All other authors have declared no conflicts of interest.