Effectiveness comparison of palbociclib, ribociclib and abemaciclib in patients with HR+/HER2- aBC: Updated results from the real-world, Italian study PALMARES-2.

Abstract

1074 Background: The Cyclin Dependent Kinase 4/6 inhibitors (CDK4/6i) Palbociclib (P), Ribociclib (R) and Abemaciclib (A) combined with Endocrine Therapy (ET) are the standard 1 st line therapy for patients (pts) with Hormone Receptor positive, Human Epidermal growth factor Receptor 2-negative, advanced Breast Cancer (HR+/HER2- aBC). However, based on conflicting results of large real-world (RW) studies (Vernieri C et al. Abstr 1014, ASCO 2024; Rugo H et al. PS2-03, SABCS 2024), it remains unclear whether P, R and A are similarly effective. Methods: PALMARES-2 is a multicenter, observational Italian RW study comparing the effectiveness of 1 st line P, R or A in female pts with HR+/HER2- aBC. The primary endpoint is overall survival (OS); RW progression-free survival (rwPFS) and time to chemotherapy (TTC) are secondary endpoints. rwPFS, TTC and OS were defined as the time between 1 st line ET+CDK4/6i initiation and disease progression/death, initiation of 1 st chemotherapy line/death, or patient death, respectively. We used Inverse Probability of Treatment Weighting (IPTW) to balance 14 prognostic covariates related to patients (age, ECOG PS, menopausal status), tumor biology (ER, PgR, HER2, Ki67, grading, histology, endocrine sensitivity/resistance/ de novo metastatic) and metastatic sites (liver, bone, lung, serosal) in P, R and A cohorts. Effectiveness comparisons were reported as adjusted Hazard Ratio (aHR) and 95% confidence interval (CI). Results: With a cutoff date of Jan 10 th , 2025, we enrolled 3598 pts, of whom 1392 (38.7%), 1408 (39.1%) or 798 (22.2%) received P, R or A, respectively. Pts receiving A were more likely to have endocrine-resistant disease, liver metastases and lower PgR expression, and less likely to have de novo metastatic disease (p < 0.001). Median follow-up was shorter in R/A cohorts (31.8/29.6 months) than in the P cohort (52.4 months). Median rwPFS, TTC and OS in the whole population were 26.1, 39.4 and 67.1 months, respectively. After IPTW adjustment, R and A were associated with better rwPFS and TTC when compared to P, while only R was associated with better OS (Table). R and A did not show significant rwPTS, TTC or OS differences (Table). Conclusions: The three CDK4/6i have different effectiveness in HR+/HER2- aBC pts. Longer follow-up of PALMARES-2 study and more pts/events in the A cohort are needed to perform definitive OS comparisons between P, R and A. P (N = 1392) R (N = 1408) A (N = 798) N° events (%) N° events (%) N° events (%) rwPFS 992 (71.2%) 711 (50.5%) 418 (52.4%) TTC 845 (60.7%) 516 (36.6%) 332 (41.6%) OS 586 (42.1%) 270 (19.2%) 189 (23.7%) R vs P: aHR (95% CI; P ) A vs P: aHR (95% CI; P ) A vs R: aHR (95% CI; P ) rwPFS 0.88 (0.80-0.97; 0.02) 0.88 (0.77-0.99; 0.04) 0.99 (0.87-1.13; 0.91) TTC 0.83 (0.74-0.94; <0.01) 0.86 (0.75-0.99; 0.04) 1.04 (0.89-1.20; 0.65) OS 0.75 (0.64-0.87; <0.01) 0.91 (0.76-1.09; 0.3) 1.21 (0.99-1.49; 0.06)