Abstract PS10-09: Real-world analysis of concomitant medication use with potential drug-drug interactions (DDI) in patients with metastatic breast cancer (MBC) treated with cylin dependent kinase (CDK) 4/6 inhibitors
Authors: Rugo Hope S. , Balu Sanjeev , Li Yunfeng , Chen Guifang , Li Xin , Turner Stuart , Sin Roxana 
Published: February 2021

Abstract
Background: In combination with endocrine therapy, the CDK4/6 inhibitors (CDK4/6i) ribociclib, palbociclib, and abemaciclib have improved progression free survival and in some cases overall survival in women with hormone receptor positive (HR+)/HER2 negative MBC. Use of concomitant medications and the potential for drug-drug interactions (DDI) is an important issue in clinical oncology, particularly among patients with MBC treated for long durations of time with CDK4/6i, and could lead to sub-optimal medication adherence or subsequent dose reductions/discontinuations. Objective: To describe concomitant medication use that could lead to DDI with CDK4/6i as well as CDK4/6i dosing, adherence, and discontinuation patterns in real-world clinical practice. Methods: Adult women with HR+/HER2- MBC initiating treatment with ribociclib, palbociclib, or abemaciclib as the first CDK4/6i (index therapy) were retrospectively identified from the Optum Clinformatics Data Mart (1/1/2017 - 9/30/2019), a large US healthcare claims database. Eligibility included 3 months of baseline (pre-index date) and at least 3 months of follow-up (post-index date) data. Concomitant medications (identified from the literature) evaluated at baseline included CYP3A inhibitors and inducers, P-glycoprotein (P-gp) inhibitors and inducers, and medications associated with risk of torsades de pointes (TdP). Treatment persistence was analyzed using Kaplan-Meier (KM) as time from index date to discontinuation, defined as an interruption of at least 90 consecutive days of the index treatment or end of patient enrollment or switch to another medication. Adherence was measured by proportion of days covered (PDC), using the recommended administration schedule of 21 days of treatment followed by 7 days off. Results: A total of 2,994 women were included: 184 initiated ribociclib as first CDK4/6i; 2,550 palbociclib; and 260 abemaciclib. Median duration of follow-up was 13.7 [Interquartile range (IQR)] 11.8); 13.1 (IQR 13.5); and 9.3 (IQR 9.2) months. The majority in each cohort were postmenopausal (ribociclib: 89.1%; palbociclib: 92.8%; abemaciclib: 90%) and received the index CDK4/6i as &gt; 2nd line of therapy (ribociclib: 81.5%; palbociclib: 87.6%; abemaciclib: 88.9%). Mean age (66.4; 66.8; and 65.3 yrs) and National Cancer Institute comorbidity index [mean/SD: 1.2 (1.6); 1.2 (1.7); 1.1 (1.6)] were similar for the ribociclib, palbociclib, and abemaciclib cohorts, respectively. Patients with ≥ one concomitant medication (60.3%; 64.2%; 65.8%) and those with &gt; one medication associated with TdP (57.1%; 59.4%; 61.9%) were similar for the 3 cohorts. The CDK4/6i discontinuation rates, starting dose, dose reduction, and adherence results are listed below (Table). Conclusions: Use of concomitant medications that could lead to a DDI with a CDK4/6i, especially those with risk of TdP, CDK4/6i treatment discontinuation, and adherence was similar between ribociclib, palbociclib, and abemaciclib in this real-world retrospective descriptive study. More patients in the ribociclib cohort maintained starting dose and less decreased to &lt;50% of the starting dose compared to palbociclib and abemaciclib, although the cohort is small. Results are limited by the relatively smaller number in the ribociclib and abemaciclib cohorts.
Descriptive analysis on characteristics in follow up period by index drug groupRibociclib (N = 184)Palbociclib (N = 2550)Abemaciclib (N = 260)Discontinuation of Index Treatment, n (%)96 (52.2)1266 (49.7)123 (47.3)Starting dose, mean (SD)532.6 (141.1)118.5 (13.4)287.7 (56.6)Patients with first time dose changeNo change during the entire follow up period, n (%)148 (80.4)1740 (68.2)176 (67.7)Decrease &gt; 50%, n (%)7 (3.8)0 (0)5 (1.9)Decrease ≤ 50%, n (%)20 (10.9)773 (30.3)68 (26.2)Adherence (PDC), mean (SD)0.85 (0.2)0.87 (0.2)0.87 (0.2)
Citation Format: Hope S. Rugo, Sanjeev Balu, Yunfeng Li, Guifang Chen, Xin Li, Stuart Turner, Roxana Sin. Real-world analysis of concomitant medication use with potential drug-drug interactions (DDI) in patients with metastatic breast cancer (MBC) treated with cylin dependent kinase (CDK) 4/6 inhibitors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-09.