Real-world data on the effectiveness and toxicity of CDK 4/6 inhibitors combined with hormonal therapy in patients with metastatic hormone receptor-positive and HER2-negative breast cancer in first- and second-line treatments within the Costa Rican h

e13053 Background: Standard first- and second-line treatments for advanced or metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) breast cancer involve combining anti-estrogen therapy with CDK4/6 inhibitors (CDK4/6i). However, head-to-head comparisons of CDK4/6 inhibitors in real-world settings are limited. To our knowledge, this is the first study from Central America to evaluate the effectiveness and safety of ribociclib and palbociclib in this context. Methods: This retrospective, multicenter study included 220 patients with HR+/HER2- metastatic breast cancer treated with CDK4/6 inhibitors (ribociclib or palbociclib) and anti-hormonal therapy between 2017 and 2021. Data from Costa Rican healthcare institutions, including Hospital Calderón Guardia, Max Peralta, Hospital México, and San Juan de Dios, provided real-world insights into treatment outcomes. Results: Among the 220 patients, 65% received palbociclib and 35% ribociclib. In first-line treatment, ribociclib achieved a median progression-free survival (PFS) of 29.8 months (95% CI: 23.1–37.5) compared to 28.4 months (95% CI: 21.2–34.6) with palbociclib. The median overall survival (OS) was 46.7 months (95% CI: 31.5–59.3) for ribociclib versus 40.2 months (95% CI: 32.1–52.8) for palbociclib. In second-line treatment, ribociclib showed a median PFS of 14.2 months (95% CI: 10.1–20.5), while palbociclib achieved 12.5 months (95% CI: 9.3–18.1). The median OS was 31.4 months (95% CI: 20.7–45.6) for ribociclib versus 27.1 months (95% CI: 18.5–36.2) for palbociclib. Patients receiving palbociclib in first-line treatment had significantly better OS compared to second-line use (40.2 vs. 27.1 months; HR 1.47; p = 0.048). Ribociclib showed a trend toward improved OS in first-line treatment (46.7 vs. 31.4 months; HR 1.22; p = 0.092), though not statistically significant. Overall, no significant differences in PFS or OS were observed between ribociclib and palbociclib. However, ribociclib showed a trend toward longer survival. Both drugs demonstrated comparable safety profiles. Neutropenia was the most common adverse event, leading to dose reductions in 16% of patients. Importantly, dose reductions did not impact survival outcomes. Conclusions: This study provides the first regional evidence of the effectiveness and safety of ribociclib and palbociclib in metastatic HR+/HER2- breast cancer. The data suggest that if palbociclib is used, it should ideally be initiated in the first-line setting to optimize clinical benefit. Continued research and regional data are crucial for refining treatment strategies.