Real-World Clinical Experience of First-Line Ribociclib Combined with an Aromatase Inhibitor in Metastatic Breast...

Despite initial sensitivity to ET, most patients with HR+/HER2- breast cancer develop resistance. A key molecular mechanism of endocrine resistance in HR+ breast cancer involves dysregulation of the cyclin D-CDK4/6-Rb signaling axis, which controls the transition from the G1 to S phase of the cell cycle. Introducing cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) has changed therapeutic paradigms in HR+/HER2- breast cancer, as their synergistic use with endocrine therapy significantly prolongs progression-free survival (PFS) and effectively mitigates clinically relevant endocrine resistance in this patient population compared to ET alone. The aim of our study was to evaluate patients' clinical characteristics, the clinical effectiveness of treatment, measured by progression-free survival (PFS), and the safety profile of combined ribociclib (CDK4/6i) and standard endocrine therapy (aromatase inhibitor) as a first-line treatment for patients with HR+/HER2- advanced or metastatic breast cancer at the Clinic of Oncology, University Clinical Centre Nis, Serbia.

In this study, we present a retrospective prospective analysis of all patients with metastatic HR+/HER2- breast cancer treated with a combination of ribociclib and aromatase inhibitors in the first-line treatment of metastatic HR+/HER2- BC between June 2022 and January 2025, with a follow-up completed in October 2025. A total of 132 patients who met the criteria were included.

The median progression-free survival (PFS) in the entire group was 30 months, while the 12-, 24-, and 36-month PFS were 82.15%, 72.24%, and 28.75%, respectively. The overall response rate (ORR) was 41.7%, while the clinical benefit rate (CBR) was 89.3%. There was no statistically significant difference in PFS with respect to tumor grade (p = 0.54), Ki 67 level (<20% vs. >20%, p = 0.83), or the type of adjuvant endocrine therapy used (tamoxifen vs. AI) It is important to emphasize that female patients who had not previously received chemotherapy had a better response to ribociclib compared to those who had (33 m vs. 28 m, p = 0.05). Although a numerical difference in PFS was found in patients with bone-only metastases compared to those with metastases in other organs, the difference was not statistically significant (PFS 33 m vs. 30 m, p = 0.27;), and efficacy was consistent across menopausal status groups. The most common adverse effect was neutropenia, occurring in 89.4% of patients, 47.7% of whom presented with grade 3 or 4. As for hepatotoxicity, transaminase increase occurred in 25 patients (18.8%), 5 of whom (3.8%) were grade 3-4, and QTc interval prolongation occurred in 5.3% of patients.

The results in terms of PFS and AEs are consistent with those of pivotal studies and real clinical practice data, but a direct comparison is not possible due to differences in patient populations. Ribociclib once again demonstrated efficacy in all patient subgroups and remains the gold standard, alongside ET, for first-line HR+/HER2-negative mBC.