Abstract P5-11-07: Real-world predictors of first-line treatment and descriptive outcomes in HR+/HER2− metastatic breast cancer patients in the US
Authors: Downer MK , Jhaveri Komal , Bardia Aditya , Loi Sherene , Kent Matthew , Luhn Patricia , Humke Eric W. 
Published: March 2020

Abstract
Background: Hormone-receptor positive (HR+) breast cancer (BC) includes 60-65% of all BC. While endocrine therapy (ET) is the mainstay in managing HR+ metastatic (m)BC, newer agent approvals, such as inhibitors of cyclin-dependent kinases 4/6 (CDK4/6i), mTOR and PI3K have transformed the treatment landscape, providing multiple treatment options for mBC patients. We used real-world data (RWD) to describe treatment decision-related factors and later outcomes among US patients with HR+/HER2- mBC treated in the first line (1L).
Methods: Data were acquired from the Flatiron Health electronic health record-derived database comprising de-identified patient-level data from patients diagnosed with HR+/HER2− mBC (1/1/2015-11/1/2018). Multivariable logistic regression was used to estimate associations of patient characteristics with treatment choice with odds ratios (ORs) and 95% confidence intervals (CIs). Kaplan Meier methods estimated time to next treatment (TTNT) and overall survival (OS).
Results: Among 4763 patients with HR+/HER2- mBC, &gt;75% received ET in 1L. ET + CDK4/6i comprised 39.4% of regimens. ET mono was common (30.8%); chemo without ET (18.8%), ET+other (6.3%), and other regimens (4.7%) were less so. Palbociclib comprised 93.5% of CDK4/6i use; followed by ribociclib (ribo; 4.5%) and abemaciclib (abema; 2.0%). ET + CDK4/6i use increased from 13.6% to 58.7% over follow-up, coinciding with decreased use of both ET mono (50.6% to 20.1%) and chemo (20.0% to 13.8%) treatments.
Patients were significantly less likely to receive ET + CDK4/6i vs ET mono if they were older (OR[95% CI]; ≥65 vs &lt;45; 0.43 [0.29-0.64]), or had higher ECOG (≥2 vs &lt;2; 0.48[0.36-0.65]), but more likely if they had metastases beyond bone (beyond bone vs bone only; 1.15[1.00-1.39]), or were diagnosed more recently (2018 vs 2015: 5.58[4.30-7.28]; 2017 vs 2015: 3.49 [2.77-4.40]; 2016 vs 2015: 1.90[1.53-2.36]). Patients were significantly less likely to receive chemo without ET vs ET mono if they were older (≥45-&lt;65 vs &lt;45: 0.47 [0.31-0.71]; ≥65 vs &lt;45: 0.16 [0.10-0.23]) or had higher ECOG (≥2 vs &lt;2; 0.53 [0.36-0.76]), but more likely if they had metastases beyond bone (beyond bone vs. bone only; 3.75 [2.99-4.73]).
Median TTNT and OS were shortest in patients receiving 1L chemo without ET (TTNT/OS: 4.9/23.8 mo), and longest in patients receiving 1L ET + CDK4/6i (20.2/41.0 mo). ET with palbociclib vs ET with ribo or abema appeared to rendered longer TTNT (20.3 vs 12.5 mos or N/A, respectively) and OS (41.0 vs N/A or 21.0 mo), but few patients received ribo or abema, making inferences challenging.
Conclusions: ET + CDK4/6i was increasingly common therapy for 1L treatment of patients with HR+/HER2- mBC, while chemo and ET mono use decreased. Physicians tended to prescribe ET + CDK4/6i instead of ET mono if patients were younger, had lower ECOG, and had metastases beyond bone. Limitations include missingness and residual confounding inherent in RWD, and small sample size in certain regimens. This RWD support the potential ability of ET + CDK4/6i’s to extend TTNT and OS over ET mono as seen in randomized clinical trials.
Table 1. Associations between patient characteristics at diagnosis and 1L treatment choice among mBC patients diagnosed between 1/1/2015 and 11/1/2018.ET MonoChemo without ETET + CDK4/6iNMultivariable OR (95% CI)1NMultivariable OR (95% CI)1NMultivariable OR (95% CI)1Age (years)&lt;4555NA (ref)1041.00 (Ref)1131.00 (Ref)≥45 - &lt;654254530.47 (0.31-0.71)8401.00 (0.66-1.50)≥659893370.16 (0.10-0.23)9230.43 (0.29-0.64)RaceWhite1033NA (ref)5981.00 (Ref)13311.00 (Ref)Non-White2992261.12 (0.88-1.41)3590.88 (0.72-1.08)mBC TypeRecurrent982NA (ref)5971.00 (Ref)12821.00 (Ref)De Novo4822961.12 (0.85-1.47)5910.96 (0.76-1.21)Mets at DiagnosisBone Only656NA (ref)1591.00 (Ref)7521.00 (Ref)Beyond Bone8037293.75 (2.99-4.73)11121.18 (1.00-1.39)ECOG&lt;2517NA (ref)4661.00 (Ref)9211.00 (Ref)≥2172700.53 (0.36-0.76)1470.48 (0.36-0.65)Stage at DiagnosisI-II541NA (ref)3531.00 (Ref)7771.00 (Ref)III-IV7514881.00 (0.76-1.30)9570.95 (0.76-1.18)Year of Diagnosis2015540NA (ref)2871.00 (Ref)3121.00 (Ref)20164602480.95 (0.74-1.23)4801.90 (1.53-2.36)20173072211.24 (0.94-1.63)5773.49 (2.77-4.40)20181621381.54 (1.10-2.14)5075.58 (4.30-7.28)1All models are mutually adjusted for all other covariates in the table
Citation Format: MK Downer, Komal Jhaveri, Aditya Bardia, Sherene Loi, Matthew Kent, Patricia Luhn, Eric W. Humke. Real-world predictors of first-line treatment and descriptive outcomes in HR+/HER2− metastatic breast cancer patients in the US [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-07.