470P - Increased risk of vertebral fractures in healthy bone in metastatic breast cancer patients treated with CDK4/6 inhibitors combined with endocrine therapy

Background

CDK4/6 inhibitors (CDK4/6-i) combined with endocrine therapy (ET) have become the standard of care for ER-positive HER2-negative metastatic breast cancer (mBC) and have significantly improved clinical outcomes. In long-term survivors, bone health is a crucial issue. The risk of fragility fractures associated to ET is well established. Preclinical data suggest that CDK4/6-i could have an effect on the bone microenvironment, however no clinical data are available. The aim of this study is to evaluate vertebral fractures (VFs) progression in mBC patients (pts) treated with CDK4/6-i combined with ET.

Methods

A series of 211 ER-positive HER2-negative mBC pts treated with CDK4/6-i combined with ET and referred to Medical Oncology and Breast Unit of ASST Spedali Civili, Brescia, from 2017 to 2023 were enrolled. VFs were evaluated through CT scan at baseline and at subsequent CT restaging and were classified as mild, moderate and severe based on Genant classification.

Results

All pts were female, with a median age of 55.5 years (32-79). CDK4/6-i were administered as first, second and third line of treatment in 113 (53.6%), 65 (30.8%) and 6 (2.9%) pts, respectively. ETs were aromatase inhibitor and fulvestrant in 104 (49.3%) and 107 (50.7%) pts, respectively. At baseline, 141 patients (66.8%) had bone metastases. 102 (48.3%) pts were treated with bone-targeted agents (BTAs). VFs in healthy bone were detected in 22 (10.4%) pts at baseline and in 37 (17.5%) pts after a mFU of 24 months (p<0.001), with 21 (10.1%) pts experiencing VFs progression, defined as the onset of a new VF of the worsening of pre-existing VFs. Among pts receiving BTAs, VFs in healthy bone were detected in 6 (5.9%) pts at baseline and in 16 (15.7%) pts after a mFU of 24 months (p = 0.006). Correlations between fracture risk factors and VFs progression as well as the comparison between patients receiving and patients not receiving BTAs will be presented at the meeting.

Conclusions

These data suggest a detrimental effect of CDK4/6-i and ET combination on bone health. Studies with a prospective design, a control arm with ET alone and longer follow-up are needed to better explore this issue.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

R. Pedersini: Financial Interests, Institutional, Advisory Board: Novartis, Lilly, Amgen, Gilead, Daiichi Sankyo, Roche, Eisai, Seagen. A. Berruti: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Janssen, IPSEN; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker, Public speaking in international webinar: HRA; Financial Interests, Institutional, Funding: Astellas, Janssen; Non-Financial Interests, Institutional, Product Samples: Sanofi, Novartis. All other authors have declared no conflicts of interest.