Abstract PS1-11-10: Real-world progression-free survival 2 (rwPFS2) and tumor response with CDK4/6is + aromatase inhibitor (AI) in patients (pts) with HR+/HER2- metastatic breast cancer (MBC)

Abstract Background CDK4/6is, including palbociclib (PAL), ribociclib (RIB), and abemaciclib (ABE), plus endocrine therapy, have been the standard of care for first-line (1L) HR+/HER2- MBC treatment. There have been no head-to-head randomized clinical trial data comparing CDK4/6is. The Palbociclib Verifying Evidence of Real-world Impact Study (P-VERIFY) is the largest real-world comparative effectiveness study to date (N = 9146), suggesting no significant differences in overall survival (OS) and progression-free survival (PFS) between the 3 CDK4/6is plus AI. This P-VERIFY data analysis compared rwPFS2 and real-world tumor response (rwTR) between 1L PAL, RIB, and ABE plus AI for HR+/HER2- MBC. Methods P-VERIFY is a retrospective Flatiron Health Research Database analysis of pts with HR+/HER2- MBC who initiated 1L CDK4/6i + AI between Feb 2015 and Nov 2023. All 9146 pts in P-VERIFY were included for rwPFS2 analysis, while 8010 (87.6%) had at least one tumor response assessment and were eligible for rwTR. rwPFS2 was defined as the time from 1L CDK4/6i + AI initiation (index date) to disease progression on 2L treatment or death from any cause, whichever came first. rwTR was defined as the change in burden of disease over the course of 1L index treatment based on the treating clinician’s assessment of radiologic evidence. Pts were followed until death, last medical activity, or May 31, 2024 (data cut-off date). Stabilized inverse probability treatment weighting (sIPTW) was used to balance pt characteristics. KM curves and Cox regression were used to compare rwPFS2. Logistic regression was used to compare rwTR. Results After sIPTW, baseline demographics and clinical characteristics were generally balanced between treatment groups. Median rwPFS2 (95% CI) was 35.8 (34.6−37.5) months for PAL + AI, 41.7 (37.5−46.2) months for RIB + AI, and 35.6 (32.2−45.5) months for ABE + AI. There were no significant rwPFS2 differences between RIB + AI vs PAL + AI HR (95% CI) = 0.99 (0.89−1.10), ABE + AI vs PAL + AI HR = 0.95 (0.85−1.07), and ABE + AI vs RIB + AI HR = 0.97 (0.83−1.13) (all P 0.05). The best overall rwTR rates were 55.5% for PAL+AI, 57.4% for RIB+AI, and 57.4% for ABE+AI; these did not significantly differ between the 3 groups (OR = 1.08 0.95−1.23 for RIB + AI vs PAL + AI; OR = 1.08 0.94−1.25 for ABE + AI vs PAL + AI; and OR = 1.00 0.84−1.20 for ABE + AI vs RIB + AI). Clinical benefit rates were similar among PAL + AI (85.8%), RIB + AI (86.3%), and ABE + AI (86.5%). Conclusions This large real-world comparative analysis suggests that rwPFS2 and rwTR do not significantly differ between 1L RIB + AI, ABE + AI, and PAL + AI in pts with HR+/HER2− MBC. These findings align with previous P-VERIFY analyses, which also suggested no significant differences in OS and PFS among the 3 CDK4/6is for this patient group. Citation Format: H. S. Rugo, A. Brufsky, R. M. Layman, X. Liu, B. Li, L. McRoy, A. B. Cohen, M. Estevez, P. Cottu, M. Thill, G. Curigliano. Real-world progression-free survival 2 (rwPFS2) and tumor response with CDK4/6is + aromatase inhibitor (AI) in patients (pts) with HR+/HER2- metastatic breast cancer (MBC) 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 PS1-11-10.