Concurrent Use of Medications with Potential Drug–Drug Interactions: Real-World Analysis of Patients Treated with CDK4/6 Inhibitors

In this real-world retrospective study, more patients in the ribociclib cohort compared with palbociclib and abemaciclib maintained starting doses and fewer patients decreased to <50% of the starting dose.

When prescribed in combination with endocrine therapy, the CDK4/6 inhibitors, such as abemaciclib, palbociclib, and ribociclib, have advanced progression-free survival, and, at times, improved cases of overall survival in women with hormone receptor–positive, HER2-negative metastatic breast cancer.

A significant challenge in clinical oncology is the use of concomitant medications and the potential for drug–drug interactions, particularly among patients with metastatic breast cancer who are receiving treatment for extended periods of time with CDK4/6 inhibitors, potentially contributing to adherence issues or the need for dose reduction or treatment discontinuation.

In this study, Hope S. Rugo, MD, FASCO, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, and co-investigators analyzed real-world data to ascertain whether concomitant medication use could contribute to drug–drug interactions and potential issues with discontinuation, adherence, and dosing.

Adult women with hormone receptor–positive, HER2-negative metastatic breast cancer initiating treatment were retrospectively identified from a large US healthcare claims database from January 1, 2017, to September 30, 2019. These patients had received treatment with abemaciclib, palbociclib, or ribociclib as the first CDK4/6 inhibitor therapy (index therapy).

To be included in this trial, patients required 3 months of baseline data as well as a minimum of 3 months of follow-up data. Cytochrome P4503A (CYP3A) inhibitors and inducers, P-glycoprotein inhibitors and inducers, and medications associated with risk for torsades de pointes were considered concomitant medications that should be assessed and included at baseline.

Treatment discontinuation was defined as an interruption of at least 90 consecutive days of the index treatment, end of patient enrollment, or switch to another medication. Adherence was characterized as the proportion of days covered, using the recommended administration schedule of 21 days of treatment followed by 7 days off.

A total of 2994 women were included in the study who had received treatment with a CDK4/6 inhibitor: 260 initiated with abemaciclib, 2550 initiated with palbociclib, and 184 initiated with ribociclib. Follow-up median duration was 13.7 months.

Similar characteristics were shared across treatment groups with abemaciclib, palbociclib, and ribociclib: the majority of patients were postmenopausal (90%, 92.8%, and 89.1%, respectively); had received the index CDK4/6 inhibitor as greater than second-line therapy (88.9%, 87.6%, and 81.5%, respectively); had a National Cancer Institute Comorbidity Index (mean [standard deviation]: 1.1 [1.6], 1.2 [1.7], and 1.2 [1.6], respectively); had a mean age of 65.3 years, 66.8 years, and 66.4 years, respectively; use of ≥1 concomitant medications (65.8%, 64.2%, and 60.3%, respectively); use of >1 medication associated with torsades de pointes (61.9%, 59.4%, and 57.1%, respectively); and discontinuation rates of the CDK4/6 inhibitor (47.3%, 49.7%, and 52.2%, respectively). Adherence was also comparable for all 3 CDK4/6 inhibitors.

In this real-world retrospective descriptive study, there was similarity among the abemaciclib, palbociclib, and ribociclib groups with concomitant medication use leading to drug–drug interactions with a CDK4/6 inhibitor, especially in those with risk for torsades de pointes, CDK4/6 inhibitor treatment discontinuation, and adherence. Although the cohort was small, more patients in the ribociclib cohort maintained starting doses and fewer decreased to <50% of the starting dose compared with palbociclib and abemaciclib. The relatively small size of the ribociclib and abemaciclib study cohorts resulted in limitations in extrapolation from these cases.

Source: Rugo HS, Balu S, Li Y, et al. Real-world analysis of concomitant medication use with potential drug-drug interactions (DDI) in patients with metastatic breast cancer (MBC) treated with cyclin dependent kinase (CDK) 4/6 inhibitors. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS10-09.