AN OBSERVATIONAL STUDY OF CARDIAC EVENTS IN PATIENTS WITH HER2- POSITIVE METASTATIC BREAST CANCER WHO HAVE A LEFT VENTRICULAR EJECTION FRACTION (LVEF) BETWEEN 40%-49% PRIOR TO INITIATING TREATMENT WITH KADCYLA®

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  TRASTUZUMAB EMTANSINE
• Medical condition to be studied:
  Left ventricular dysfunction

Population studied

• Short description of the study population:
  The source population is the overall population reported in the EHR and managed in at least one of the U.S. oncology clinics taking part in the Flatiron health network from 01 January 2011 onwards.; Patients were included if they fulfill each of the following inclusion criteria:; 1. Diagnosis of breast cancer (ICD-9 174.x or ICD-10 C50.x) and pathology confirmed by medical chart review. At least two visits in the EHR database on or after 01 January 2011 (in order to exclude patients not actually followed in clinical practice).; 2. Initiating Kadcyla® treatment after the date of metastatic breast cancer diagnosis (confirmed by medical charts review).; 3. Evidence of LVEF < 50% within 60 days prior to initiation of Kadcyla®.
• Age groups:
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Breast Cancer patients
• Estimated number of subjects:
  0

Study design details

• Main study objective:
  To describe the risk of cardiac dysfunction in a population of patients with metastatic breast cancer and a low LVEF (40-<50%), within 60 days prior to initiating Kadcyla.
• Outcomes:
  - Left ventricular ejection fraction (LVEF) values by time - The incidence rate and the cumulative incidence of LVEF decrease greater than 10% points from baseline, Congestive heart failure (CHF) event rate, incidence rate and cumulative incidence of CHF event observed during cohort’s follow-up. Relevant subgroup at risk will be analyzed separately to estimate CHF incidence rate and respective cumulative incidence. Event rate, incidence rate and their respective cumulative incidence will also be estimated for each of the other cardiac events of interest.
• Data analysis plan:
  Analyses will be performed two times including one interim analysis and one final analysis.Categorical variables will be summarized using absolute frequencies and percentages, and continuous variables will be summarized using descriptive statistics (i.e. mean, median, standard deviation and range), separately for the whole study population and by relevant subgroups (e.g. patients with and without CHF at baseline). All statistical analyses will be performed in-house using Statistical Analysis System (SAS) 9.X or R.