Renata Duchnowska, Katarzyna Soter, Katarzyna Pogoda, Jolanta Smok-Kalwat, Aleksandra Grela-Wojewoda, Karolina Winsko-Szczęsnowicz, Agnieszka Kowalewska-Felczak, Marek Szwiec, Iwona Danielewicz, Joanna Streb, Tomasz Lewandowski, Bartosz Szymanowski, Joanna Kiszka, Barbara Radecka, Ewa Kalinka‐Warzocha, Bartosz Kamil Sobocki, Maria Litwiniuk, Aleksandra Łacko, A Balata, Justyna Żubrowska, Marek Ziobro, Bogumiła Czartoryska-Arłukowicz, Rodryg Ramlau, Paulina Myśliwiec, Paulina Lipiec, Michał Jurczyk, Grzegorz Kade, Magdalena Łobaza, Joanna Hudała-Klecha, Magdalena Szymanik-Resko, Ewa Kustra, Anna Koriat-Błońska, Bartłomiej Tomasik, Michał Bieńkowski, Jacek Jassem
BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the standard first- and second-line treatments for hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Real-world data (RWD) may inform the optimal use of these agents in routine practice. PATIENTS AND METHODS: The multicenter, population-based POLiCDK study compared progression-free survival (PFS), second PFS, and overall survival (OS) in ABC patients with HR+/HER2- ABC treated with palbociclib (PAL), ribociclib (RIB), or abemaciclib (ABE) in first- or second-line ET settings at 16 Polish centers between September 2017 and January 2025. Analyses were stratified by endocrine sensitivity/resistance, and stabilized inverse probability of treatment weighting was used to balance baseline characteristics. RESULTS: Among 2063 patients (701 PAL, 968 RIB, 394 ABE), 1583 (76.7 %) received CDK4/6i in the first-line and 480 (23.3 %) in the second-line setting. Overall, 927 (44.9 %) had de novo ABC; 819 (39.7 %) were endocrine-naïve, 158 (8.9 %) primary resistant, and 808 (39.2 %) secondary resistant. Median follow-up was 35.9, 24.1, and 21.4 months for PAL, RIB, and ABE, respectively. In endocrine-naïve patients, PFS did not differ significantly between CDK4/6i combined with aromatase inhibitors (AIs). In secondary endocrine-resistant disease, RIB and ABE outperformed PAL with AI combinations, whereas outcomes with fulvestrant were similar. In second-line therapy, all three CDK4/6i showed comparable results. Adjusted hazard ratios confirmed these trends without consistent superiority of any single agent. CONCLUSIONS: Endocrine sensitivity/resistance and ET partner were major determinants of outcome with CDK4/6i plus ET in HR+/HER2- ABC, informing individualized treatment selection and sequencing.