Abstract PO4-18-02: Real-world (RW) utilization and patient outcomes across three CDK4/6 inhibitors in metastatic breast cancer (mBC)
Authors: Weipert Caroline , Wander Seth , Davis Andrew , Bucheit Leslie , Saha Jayati , Liao Jiemin , Zhang Nicole , Stover Daniel , Bardia Aditya , Cristofanilli Massimo 
Published: May 2024

Abstract
Background: While CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is standard-of-care first-line (1L) therapy for hormone-positive (HR+), HER2-negative mBC, there is ongoing debate regarding optimal use of the three FDA-approved CDK4/6i drugs. All three drugs have demonstrated significantly improved progression-free survival (PFS), but only two have significantly improved overall survival (OS). These trial data have prompted debate regarding optimal selection and sequencing of these drugs. To further evaluate this, we analyzed a RW clinical-genomic database to explore the use and outcomes associated with each of these CDK4/6i drugs.
Methods: RW data were queried using GuardantINFORM, a database combining de-identified genomic results from patients (pts) with cell-free circulating tumor (ctDNA) testing done via Guardant360, with administrative claims data. Pts with BC who had record of metastatic diagnosis, &gt;2 medical or pharmacy claims, and CDK4/6i treatment in the mBC setting between March 2018 and March 2023 were included. In the subset of pts treated with CDK4/6i in the 1L or 2nd line (2L) with at least 12 months of follow-up (f/u) post-CDK4/6i initiation, RW time to next treatment (rwTTNT) and RW time to treatment discontinuation (rwTTD) were used as proxies for PFS. RW overall survival (rwOS), rwTTNT and rwTTD were reported in months (mos) and were measured based on time from first CDK4/6ki treatment claim. Multivariate Cox regressions adjusted for pt age, gender, weighted comorbidity score (Elixhauser Comorbidity Index [ECI]), and year of CDK4/6i start were used to compare outcomes across CDK4/6i drugs. Chi-squared tests were used for comparison of categorical variables, while one-way ANOVA was used for continuous variables.
Results: 4556 pts with mBC were included, of whom 65% received palbociclib (palbo), 24% abemaciclib (abema) and 11% ribociclib (ribo). Ribo use increased post-2020, while palbo use decreased and abema remained similar (2020: ribo: 9%, palbo: 63%, abema: 28%; 2022: ribo: 18%, palbo: 54%, abema: 28%). Pts who received ribo were younger and had fewer comorbidities than those receiving palbo and abema [median age: 57, 61, 60 years, respectively (p &lt; 0.001); ECI score: 19.8, 20.1, 21.3, respectively (p &lt; 0.001)]. Median f/u for pts included in outcomes assessment was 24.1 mos for abema, 30.1 mos for palbo, and 28.5 mos for ribo. Adjusted hazard ratios (HR) for rwTTD, rwTTNT, and rwOS for pts treated in the 1L or 2L showed no significant difference between the drugs (Table 1). 1120 pts had ctDNA analysis within +/- 90 days of CDK4/6i treatment end and these data will be shown at the time of presentation.
Conclusions: RW analysis shows increased use of ribo and decreased use of palbo in recent years, with potential preferential use of ribo in pts who are younger and have fewer comorbidities. Multivariate Cox regressions adjusted for pt age, gender, co-morbidities, and year of CDK4/6i start found no significant differences in rwTTD and rwTTNT for pts treated in the 1L or 2L between the drugs. While we only included pts with at least 12 months of f/u in the outcomes analysis, it is difficult to make conclusions regarding rwOS data as the median f/u still differs between the drugs at this time. These findings confirm anecdotal evidence suggesting shifting physician preferences in the use of the CDK4/6i drugs in mBC. Further investigation is needed to refine CDK4/6i drug selection in the rapidly changing mBC landscape.
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Citation Format: Caroline Weipert, Seth Wander, Andrew Davis, Leslie Bucheit, Jayati Saha, Jiemin Liao, Nicole Zhang, Daniel Stover, Aditya Bardia, Massimo Cristofanilli. Real-world (RW) utilization and patient outcomes across three CDK4/6 inhibitors in metastatic breast cancer (mBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-02.