A Real-world Analysis of Concomitant Medication Use Among Metastatic Breast Cancer Patients Treated With CDK4/6 Inhibitors

This is a retrospective cohort study to assess the real-world analysis of concomitant medication use among metastatic breast cancer patients treated with CDK4/6 inhibitors utilizing the US Optum research administrative claims database.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Ribiciclib; Drug: Palbociclib; Drug: Abemaciclib

Detailed Description

This is a retrospective cohort study utilizing the US Optum research administrative claims database. Adult female patients who had HR+/HER2- mBC were identified and included in the study. These patients were stratified into three cohorts based on the first CDK4/6i received (ribociclib, palbociclib, or abemaciclib).

• Study period: Period during which all relevant medical and pharmacy information in the database was retrieved
• Index event identification period: time frame during which index treatment was identified
• First CDK4/6i: the date on which patients initiated their first treatment after being diagnosed with HR+/HER2- mBC; this date was considered as the index date
• Baseline period: Time frame during which patient characteristics, prior mBC treatments, and concomitant treatments received by CDK4/6i-naïve patients were evaluated
• Follow-up period: time frame on and after the index date during which patients' treatments and dosing patterns were observed

Establishment of baseline period Health plan enrollment in the three months prior to the index treatment was included in the baseline period. Patient demographics, clinical characteristics, National Cancer Institute (NCI) comorbidity index, concomitant medication use that can potentially lead to a DDI, and other BC treatments prior to the index treatment were evaluated during this period.

Establishment of follow-up period Patients were observed for ≥3 months starting from the index date until the end of the study period or continuous enrollment or until the time when patients switched to another therapy (including another CDK4/6i), whichever came first. Dosing patterns for CDK4/6i were evaluated in the follow-up period. Analyses were conducted at key time points of 3, 6, and 12 months

• Study Type: Observational
• Enrollment (Actual): 4650

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • East Hanover, New Jersey, United States, 07936
      • Novartis Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Study analyses were conducted among adult women with HR+/HER2- mBC receiving ribociclib, palbociclib, or abemaciclib, regardless of the line of therapy. Patients were identified from the US Optum Claims Data.

Description

Inclusion Criteria:

• Treated with CDK4/6i from 2015-02-01 to 2019-06-30
• ≥2 claims with a BC diagnosis recorded ≥30 days apart from the index date
• ≥2 claims with an mBC diagnosis, with a time interval between the first BC diagnosis date and the first mBC diagnosis date no longer than 30 days
• Female patients aged ≥18 years
• Continuous health plan enrollment for ≥3 months prior to the index date and ≥3 months post-index date

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ribociclib; Participants who initiated CDK4/6i therapy	Drug: Ribiciclib; Participants who initiated CDK4/6i therapy
Palbociclib; Participants who initiated CDK4/6i therapy	Drug: Palbociclib; Participants who initiated CDK4/6i therapy
Abemaciclib; Participants who initiated CDK4/6i therapy	Drug: Abemaciclib; Participants who initiated CDK4/6i therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with a prescription fill of ribociclib, palbociclib, or abemaciclib	Distribution of patients with a prescription fill of ribociclib, palbociclib, or abemaciclib at index treatment date will be present by frequency among all patients treated with CDK4/6	Index date (defined as the prescription fill for ribociclib, palbociclib, or abemaciclib for the first time)
Number of participants who took concomitant medications in baseline period, by drug name	Number of patients taking a concomitant medication/s during baseline period that can potentially lead to a drug-drug interactions (DDI) with a CDK4/6 inhibitor use with each CDK4/6 inhibitor in the follow-up period.	Baseline period (3 months)
Number of participants who took concomitant medications in follow-up period, by drug name	Number of patients taking a concomitant medication/s during baseline period that can potentially lead to a drug-drug interactions (DDI) with a CDK4/6 inhibitor use with each CDK4/6 inhibitor in the follow-up period.	From index date (defined as the prescription fill for ribociclib, palbociclib, or abemaciclib for the first time) to the end of follow-up period (12 months post index date)
Number of participants with no use of concomitant medications	Adherence to concomitant medications during the baseline period was reported	Baseline period (3 months)
Number of participants with proportion of days covered (PDC) >80%	Adherence to concomitant medication during the baseline period will be assessed using the proportion of days covered (PDC): PDC = total days of filled or refilled concomitant Rx in baseline period / total number of days in baseline period	Baseline period (3 months)
Number of participants with proportion of days covered (PDC) ≤80%	Adherence to concomitant medication during the baseline period will be assessed using the proportion of days covered (PDC): PDC = total days of filled or refilled concomitant Rx in baseline period / total number of days in baseline period	Baseline period (3 months)
Number of other breast cancer medications used	Number of other breast cancer medications used in baseline period, by drug class (HR+/Endocrine, Chemotherapy, Other treatments), for breast cancer regimens was reported	Baseline period (3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean starting dose for each CDK4/6	Distribution of starting dose and mean starting dose for each CDK4/6 was reported to describe dosing and treatment patterns associated with ribociclib, palbociclib, and abemaciclib patients	From index date (defined as the prescription fill for ribociclib, palbociclib, or abemaciclib for the first time) to the end of follow-up period (12 months post index date)
Number of participants who had any dose change (increase, decrease)	Number of patients with change in dose by each CDK4/6 inhibitor (ribociclib, palbociclib, and abemaciclib) in the follow-up period was reported	From index date (defined as the prescription fill for ribociclib, palbociclib, or abemaciclib for the first time) to the end of follow-up period (12 months post index date)
Number of participants who had a dose increase	Number of patients with change in dose by each CDK4/6 inhibitor (ribociclib, palbociclib, and abemaciclib) in the follow-up period was reported	From index date (defined as the prescription fill for ribociclib, palbociclib, or abemaciclib for the first time) to the end of follow-up period (12 months post index date)
Number of participants who had a dose decrease	Number of patients with change in dose by each CDK4/6 inhibitor (ribociclib, palbociclib, and abemaciclib) in the follow-up period was reported	From index date (defined as the prescription fill for ribociclib, palbociclib, or abemaciclib for the first time) to the end of follow-up period (12 months post index date)
Number of participants discontinuing each CDK4/6i (ribociclib, palbociclib, or abemaciclib)	Rate of discontinuation of ribociclib, palbociclib, or abemaciclib in the follow-up period was reported	From index date (defined as the prescription fill for ribociclib, palbociclib, or abemaciclib for the first time) to the end of follow-up period (12 months post index date)
Median duration of treatment (in months) by each CDK4/6i (ribociclib, palbociclib, or abemaciclib)	Duration of treatment with ribociclib, palbociclib, or abemaciclib, defined as discontinuation of each index CDK 4/6 treatment during the follow-up period was reported	From index date (defined as the prescription fill for ribociclib, palbociclib, or abemaciclib for the first time) to the end of follow-up period (12 months post index date)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLEE011AUS64 from the Novartis Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 15, 2020
• Primary Completion (ACTUAL): June 15, 2020
• Study Completion (ACTUAL): June 15, 2020

Study Registration Dates

• First Submitted: November 11, 2021
• First Submitted That Met QC Criteria: November 25, 2021
• First Posted (ACTUAL): December 2, 2021

Study Record Updates

• Last Update Posted (ACTUAL): December 16, 2021
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Concomitant medication,; drug-drug interaction,; CDK4/6 inihibitor,; HR+/HER2-metastatic breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: CLEE011AUS64

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No