Evaluating Safety in Insulin-Requiring Diabetic Patients Receiving Inavolisib Plus Endocrine Therapy-Based Regimens in the Real World

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  ITOVEBI
• Anatomical Therapeutic Chemical (ATC) code:
  (L01EM06) inavolisib

  inavolisib
• Medical condition to be studied:
  Breast cancer
• Additional medical condition(s):
  PIK3CA-mutated, HR+/HER2– metastatic breast cancer; insulin-requiring diabetes (type 1 and type 2)

Population studied

• Short description of the study population:
  The study population will consist of patients from United States of America who have insulin-requiring diabetes and are in the nationwide Flatiron Health network and who have PIK3CA-mutated, HR+/HER2– metastatic breast cancer and are taking inavolisib-based regimens in the real world.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 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:
  Insulin-requiring diabetic patients (type 1 and type 2 diabetes)
• Estimated number of subjects:
  50

Study design details

• Study design:
  Retrospective cohort study using secondary electronic health record (EHR) data from Flatiron Health network evaluating PIK3CA-mutated, HR+/HER2– metastatic breast cancer patients with insulin-requiring diabetes receiving inavolisib-based regimens over a 3 to 4-year study period.
• Main study objective:
  The main objective of this study is to describe clinical and demographic characteristics of insulin-requiring patients who receive inavolisib-based regimens in the real world (e.g., inavolisib plus fulvestrant plus palbociclib, inavolisib plus fulvestrant plus ribociclib, inavolisib plus fulvestrant, etc), and to describe the safety and tolerability of inavolisib-based regimens as it relates to hyperglycemia and associated complications (including diabetic ketoacidosis).
• Setting:
  Inclusion criteria:; • Diagnosed with breast cancer International Classification of Diseases-Ninth Revision (ICD-9) (174.x or 175.x) or ICD-Tenth Revision (ICD-10) (C50.xx) ; • Diagnosed with metastatic breast cancer (mBC) on or after 11/1/24 (FDA approval of inavolisib on 10 October 2024); • ≥18 years of age at mBC diagnosis.; • HR+/HER2– (includes HER2-low and HER2-equivocal) ; • Type 1 and type 2 diabetes patients who receive insulin for at least 6 months prior to the index date; • Patients receiving an inavolisib-based regimen, abstracted from the EHR between 01 January 2026 and 31 December 2029 (allowing for up to 6 cycles of inavolisib to collect real word adverse events [rwAEs]). ; ; Exclusion criteria:; • Patients with diabetes and end organ damage (clinician notes for diabetic kidney disease, diabetic retinopathy, diabetic neuropathy, diabetic circulatory complications, diabetic foot ulcers); • Eastern Cooperative Oncology Group score = 3+; • Inavolisib-based regimens in 4L or later
• Outcomes:
  Primary; (1) Time to first diagnosis(es) of hyperglycemia following initiation of inavolisib therapy; (2) Proportion of participants with hyperglycemia ; (3) Severity of hyperglycemia as assessed by date and discharge diagnosis of hospitalizations; (4) Severity of hyperglycemia as assessed by date and results from laboratory tests (e.g., HbA1c and glucose); (5) Proportion of participants with complications from hyperglycemia ; (6) Proportion of participants who require management of hyperglycemia by changes in inavolisib dose, duration, discontinuations and holds along with concomitant medications.; ; Secondary; (7) Time to first diagnosis of stomatitis following initiation of inavolisib therapy; (8) Proportion of participants who require management of stomatitis by changes in inavolisib dose, duration, discontinuations and holds; and dates of concomitant medications.; (9) Time to first instance/diagnosis of diarrhea following initiation of inavolisib therapy; (10) Proportion of participants who require management of diarrhea by changes in inavolisib dose, duration, discontinuations and holds; and dates of concomitant medications
• Data analysis plan:
  All analyses will be descriptive in nature and there are no statistical tests of hypotheses, nor time to event outcomes.; ; In the descriptive analyses, frequencies and percentages will be reported for categorical variables. Missing values will be described as a separate category. For proportions of participants with an observed rwAE, the analyses will be conducted in several ways, by including: 1) all participants at baseline (defined as the start of the inavolisib-based regimen); 2) participants who have at least 2 visits during the inavolisib-based regimen; 3) participants who are followed up (e.g., have health care visits) during the entire inavolisib-based regimen. Medians with interquartile range (IQR), means with standard deviation (SD), minimum values, and maximum values will be reported for continuous variables.; ; Sensitivity analyses accounting for starting dose of inavolisib, line of therapy, history of diabetes, duration of insulin use, and type of diabetes (type 1 versus type 2) will be conducted, as is feasible based on sample size.