Background and Importance Breast cancer is the world’s most prevalent cancer. There are approximately 55000 new diagnosed cases per year in Italy. CDK4/6 inhibitors are targeted orally available cancer drugs. These are highly selective inhibitors of CDK4 and CDK6, serine-threonine kinases that regulate the cell cycle progression. CDK4/6 inhibitors are indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, in combination with an aromatase inhibitor or with fulvestrant in women who have received prior endocrine therapy.

Aim and Objectives To provide real-world evidence of CDK4/6 inhibitors, to analyse drug effectiveness in our hospital.

Material and Methods We included all patients diagnosed with locally advanced or metastatic breast cancer who received CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) from national marketing authorisation to 15 September 2023. Patients were stratified by drug, age, line of therapy, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and cancer staging. We assessed progression-free survival (PFS) with the Kaplan-Meier method.

Results Sixty-three patients received CDK4/6 inhibitors. 63% were treated with palbociclib, 24% with ribociclib and 13% with abemaciclib. The mean age was 65. Median PFS was 22.4 months. There was no statistically significant difference between cases treated with palbociclib and ribociclib. Median PFS in the abemaciclib group was not reached. Age older than 65 was a significant predictor for PFS benefit (median PFS 27 months). 51% were first-line treatments (median PFS 22.4 months). Beyond first-line therapy median PFS was 27 months. 49% had baseline PS of 0. PS was identified as an important prognostic factor for PFS: PS0 median PFS 22.4 months versus PS1 median PFS 15.9 months. Locally advanced breast cancer cases had worse prognosis (median PFS 13 months). We recorded 10 cases of dose reduction due to toxicity, but only one patient discontinued therapy due to treatment-limiting toxicity.

Conclusion and Relevance All CDK4/6 inhibitors are beneficial in terms of PFS: we found no significant differences among the three drugs. Toxicities were managed by dose reductions. CDK4/6 inhibitors confer PFS benefit in elderly patients with metastatic disease. We can confirm that these drugs have radically changed the treatment for metastatic breast cancer with increased rates of treatment response and PFS.

Conflict of Interest No conflict of interest.