400P - The impact of CDK4/6 inhibitors on bone health: An Italian real-world experience

Background

Palbociclib, Ribociclib and Abemaciclib, in combination with endocrine therapy (ET), are considered the first-line treatment for hormone-responsive (HR+) disease. Breast cancer frequently metastasizes to the bone with the possible occurrence of skeletal related events (SRE, pathological fractures, hypercalcemia, radiotherapy, spinal cord compression, and orthopaedic surgery).Clinical trials have demonstrated the efficacy of these combination of treatments, but there are limited data on their effect on bone endpoints: time to SRE and skeletal Progression Free Survival (PFS).

Methods

We conducted a retrospective analysis using data from patients (pts) treated with these CDK 4/6 inhibitors (CDKIs) and ET as first- or second-line therapy between July 2014 and March 2023 in 24 hospitals in Italy. Pts had bone metastases at the treatment start. We calculated the propensity weight for each patient based on baseline characteristics using the twang package to reduce selection and confounding bias in observational analyses for the evaluation of time to SRE and Skeletal PFS.

Results

We enrolled 1139 pts (Abemaciclib n=154, Ribociclib = 316, Palbocilib= 668), 562 (49.4%) treated with Denosumab, 235 (20.7%) with zoledronic acid and 341 (30%) did not receive any anti-resorptive therapy. The radiation to the bone was the most frequent SRE that occurred in the 20% of pts. After the twang propensity weight the time to SRE (95% CI) was longer in the Acid zoledronic group than denosumab (P= 0.024). The time to SRE was longer between pts treated with zoledronic acid compared to those who did not receive any bone-targeted agent (P= 0.017). Skeletal PFS (95% CI) was longer in pts treated with zoledronic acid than to Denosumab (39 [35–39] versus 27 [25-32] months, P < 0.001) and then who don’t receive therapy (39 [35–39] versus 30 [28-32] months, P < 0.001). There was no significant differences in skeletal PFS between denosumab and none therapy.

Conclusions

Our study suggests that the use of zoledronic acid may lead to a longer time to SRE and skeletal PFS compared to denosumab or no anti-resorptive therapy. These findings can be important for the management of bone metastases in pts with HR+ metastatic breast cancer. Further prospective studies are needed to confirm these results.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Pantano: Financial Interests, Speaker, Consultant, Advisor: Novartis, Gilead, Pfizer, AstraZeneca. U.F.F. De Giorgi: Financial Interests, Personal, Advisory Board: Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, EISAI, Janssen; Financial Interests, Personal, Invited Speaker: Roche, BMS, Clovis Oncology, AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi, Roche. A. Verrazzo: Financial Interests, Speaker, Consultant, Advisor: Pierre Fabre, Lilly . All other authors have declared no conflicts of interest.