Abstract PS1-08-13: A retrospective study to assess real world rates of dose modification, therapy discontinuation and treatment outcomes in patients receiving the oral CDK4/6 inhibitors Ribociclib and Palbociclib

Abstract Introduction: The oral CDK4/6 inhibitors palbociclib and ribociclib have demonstrated improved outcomes for hormone receptor positive (HR+), HER2-negative advanced breast cancer when combined with endocrine therapy in both the first- and second-line settings. In the first line setting the randomized phase Ill PALOMA-2 (palbociclib) and MONALEESA-2 (ribociclib) trials demonstrated improved progression free survival (PFS) while MONALEESA-2 also showed an improvement in overall survival rates. We aimed to examine the rates of treatment modification and cessation among patients at our cancer center receiving these agents for metastatic or unresectable advanced HR+/HER2- breast cancer. Methods: We conducted a single center retrospective review of patients treated with CDK4/6 inhibitors between 01 June 2014 and 01 June 2024. Patients who were initiated on endocrine therapy plus palbociclib or ribociclib for metastatic or unresectable advanced HR+/HER2- breast cancer within the above time frame were included. The primary endpoints were dose reductions, dose delays, and treatment cessation within the first six cycles, the secondary endpoint was PFS. Chi-squared tests were used to compare treatment modification rates between the groups, and PFS was assessed using Kaplan-Meier survival analysis. Statistical analysis was conducted using GraphPad PRISM Software. Results: A total of 84 patients were included in this study: 43 received palbociclib and 41 received ribociclib. Overall dose reduction rates were 34.8% (n=15/43) for the palbociclib group and 58.5% (n=27/41) for the ribociclib group, there was a statistically significant difference between the two groups (χ2 8.052, p=0.0045). 10/15 (66%) of patients requiring dose reductions of palbociclib had this reduction within the first six cycles, and three of these patients (n=3/10) had an additional dose reduction during the same period. 22/27 (82%) of patients requiring ribociclib dose reduction had this reduction within the first six cycles, and four of these patients (n=4/22) had an additional dose reduction during the same timeframe. Overall dose delays were 39.5% (n=17/43) for palbociclib and 58.5% (n=27/41) for ribociclib with statistical significance observed between the two groups (χ2 5.828, p=0.0158). Most of the treatment delays were in the first six cycles in both groups: 88.2% (n=15/17) of palbociclib delays and 96.3% (n=26/27) of ribociclib delays. In the first six cycles of treatment, neutropenia was the most common cause cited in both groups for dose reductions (palbociclib n=5/10, ribociclib n=17/22) and dose delays (palbociclib n=8/17, ribociclib n=17/22). Treatment discontinuation rates prior to completion of six cycles were 24.4% (n=10/41) on palbociclib and 19.5% (n=8/41) on ribociclib (χ2 0.175, p=0.676). We assessed PFS among patients receiving CDK4/6 inhibitors with an aromatase inhibitor and there was no statistical difference in PFS observed. Conclusion: The use of ribociclib in our cohort was associated with more treatment delays, dose reductions and subsequent dose reductions when compared with palbociclib. The reasons for dose reduction were in keeping with published adverse events i.e. neutropenia with both agents and hepatotoxicity with ribociclib. Survival analysis among the subset of patients receiving CDK4/6 inhibitors with an aromatase inhibitor showed no statistically significant difference in PFS. Numerical trends towards improved event free survival favored ribociclib, although this was not statistically significant, and a larger dataset may provide more information. Citation Format: C. Steele, J. Shaw, D. O'Connor, K. Dunne, D. O'Mahony, C. Murphy. A retrospective study to assess real world rates of dose modification, therapy discontinuation and treatment outcomes in patients receiving the oral CDK4/6 inhibitors Ribociclib and Palbociclib abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-08-13.