1017 Background: Endocrine therapy (ET) plus Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) is the standard 1 st line treatment for patients (pts) with Hormone Receptor-positive, Human Epidermal growth factor Receptor 2-negative, advanced Breast Cancer (HR+/HER2- aBC). ET+CDK4/6i continuation beyond progressive disease (PD) detection, plus/minus locoregional therapies, is often used in clinical practice for selected pts with oligoprogressive disease or minimal PD. However, the effectiveness of this approach has never been investigated in large studies. Methods: In this analysis of the multicenter, real-world study PALMARES-2 (NCT06805812), we evaluated clinical characteristics and outcomes in HR+/HER2- aBC pts who continued 1 st line ET+CDK4/6i after detection of PD, as defined by physicians based on clinical-radiological assessment. The primary endpoint was real-world progression-free survival (rwPFS) beyond PD, defined as the time between the detection of the first PD event during 1 st line ET+CDK4/6i and the occurrence of subsequent PD leading to definitive ET+CDK4/6i discontinuation, or patient death. We used multivariable Cox regression models to explore the association of 15 covariates with rwPFS beyond PD. We also assessed real-world overall survival (rwOS), as defined as the time between 1 st line ET+CDK4/6i initiation and patient death. Results: Of 4,236 consecutive pts who initiated ET+CDK4/6i between January 2016 and September 2024 in 27 Italian Institutions, 2,434 pts experienced a PD event. Of these pts, 454 (18.7%) continued the same ET+CDK4/6i beyond PD and underwent radiotherapy (n = 306; 67%), surgery (n = 39; 9%), other locoregional treatments (n = 28; 6%) or no local therapies (n = 81; 18%). Pts continuing ET+CDK4/6i beyond PD were more likely to be younger and premenopausal, to have higher tumor estrogen receptor (ER) and/or progesterone receptor (PgR) expression, to have bone/lymph node metastases, and less likely to have liver metastases (p < 0.05 for all covariates). Median rwPFS beyond PD was 10.5 months (95% CI: 9.7-12). At multivariable analysis, higher tumor ER (p = 0.031)/PgR (p = 0.001) or lower Ki-67 (p < 0.001) expression, better ECOG Performance Status (p = 0.009) and the use of locoregional treatments (p < 0.001) were associated with longer rwPFS beyond PD. Pts continuing ET+CDK4/6i therapy beyond PD had better median rwOS than those discontinuing it after first PD detection (71.3 and 44.7 months, respectively; p < 0.001). Conclusions: This is the largest real-world study to show the effectiveness of 1 st line ET+CDK4/6i continuation beyond PD in HR+/HER2- aBC pts. Our findings support the use of this well-tolerated and effective approach in selected pts, such as those with less biologically aggressive tumors and/or amenable to locoregional therapies. Clinical trial information: NCT06805812 .
Vernieri et al. (Wed,) studied this question.