124 Real-World Progression-Free Survival 2 and Tumor Response of CDK4/6is + Aromatase Inhibitor in Patients With HR+/HER2– Metastatic Breast Cancer

Background

CDK4/6 inhibitors (CDK4/6i), including palbociclib, ribociclib, and abemaciclib, plus endocrine therapy, are the standard first-line treatment for hormone receptor–positive (HR+)/HER2-negative (HER2–) metastatic breast cancer. There have been no head-to-head randomized clinical trial data comparing CDK4/6is in patients with HR+/HER2− metastaic breast cancer. 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 aromatase inhibitor (AI). This P-VERIFY data analysis compared real-world progression-free survival 2 (rwPFS2) and real-world tumor response (rwTR) between first-line palbociclib, ribociclib, and abemaciclib plus AI for HR+/HER2– metastatic breast cancer.

Methods

P-VERIFY is a retrospective Flatiron Health Research Database analysis of patients with HR+/HER2– metastatic breast cancer who initiated first-line CDK4/6i plus AI between February 2015 and November 2023. All 9146 patients 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 the start of first-line CDK4/6i plus AI initiation (index date) to disease progression on second-line treatment or death from any cause, whichever came first. rwTR was defined as the change in burden of disease over the course of first-line index treatment based on the treating clinician’s assessment of radiologic evidence. Patients 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 patient 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 (Table). Median rwPFS2 was 35.8 months for palbociclib plus AI, 41.7 months for ribociclib plus AI, and 35.6 months for abemaciclib plus AI. No significant rwPFS2 differences were observed between groups (hazard ratio, 0.95–0.99; all P >.42). The best overall rwTR rates were 55.5% for palbociclib plus AI, 57.4% for ribociclib plus AI, and 57.4% for abemaciclib plus AI and did not significantly differ between the 3 groups (OR, 1.00–1.08; all P >.26). Clinical benefit rates were similar among palbociclib plus AI (85.8%), ribociclib plus AI (86.4%), and abemaciclib plus AI (86.5%).

Conclusions

This large real-world comparative analysis suggests that rwPFS2 and rwTR do not significantly differ between first-line ribociclib plus AI, abemaciclib plus AI, and palbociclib plus AI in patients with HR+/HER2− metastatic breast cancer. 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.

ClinicalTrials.gov Identifier: NCT06495164

Funding Source: Pfizer Inc, USA.

Acknowledgment: Medical writing support, conducted in accordance with Good Publication Practice (GPP3) and the International Committee of Medical Journal Editors (ICMJE) guidelines, was provided by Michael Riley, PhD of Oxford PharmaGenesis Inc, Wilmington, DE, USA with funding provided by Pfizer Inc, USA.