Treatment of Canadian Men and Pre/Peri/Post-menopausal Women With ER+ Advanced Breast Cancer in the Real-World Setting With Hormone Therapy ± Targeted Therapy (Treat ER+ight)

Treatment of Canadian Men and Pre/Postmenopausal Women With ER+ Advanced Breast Cancer in the Real-World Setting With Hormone Therapy ± Targeted Therapy

Although randomized controlled trials (RCTs) provide evidence of efficacy, generalization of these results to patients in the real-world setting is challenging, given RCTs are conducted in highly selected patient populations.

An understanding of the effectiveness of approved cancer therapies in routine clinical practice is essential in order to optimize the management of these patients and to identify treatment and monitoring gaps.

This is the first Canadian study to describe real-world treatment patterns/sequencing, effectiveness and monitoring for men and pre/postmenopausal HR+ HER2- advanced breast cancer patients. This registry incorporates an observational prospective cohort design and will enroll 500 men and pre/postmenopausal HR+ HER2- advanced breast cancer women that have been exposed to endocrine therapy (ET) or ET in combination with targeted therapy (TT) including patients receiving CDK4/6 inhibitor therapy combinations..

Study Overview

• Status: Completed
• Conditions: HR+ HER2- Men, Pre/Postmenopausal Advanced Breast Cancer
• Intervention / Treatment: Drug: Endocrine therapy may include one of the following therapies: letrozole, anastrozole, exemestane, tamoxifen or fulvestrant; Drug: Endocrine therapy in combination with targeted therapy may include: everolimus plus exemestane or CDK4/6 inhibitor plus endocrine therapy

• Study Type: Observational
• Enrollment (Actual): 440

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1S 4L8
    • Novartis Investigative Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Novartis Investigative Site
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 2X6
      • Novartis Investigative Site
    • North Vancouver, British Columbia, Canada, V7L 2L7
      • Novartis Investigative Site
    • Richmond, British Columbia, Canada, V7C 5L9
      • Novartis Investigative Site
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Novartis Investigative Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Novartis Investigative Site
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Novartis Investigative Site
  • Ontario
    • Cambridge, Ontario, Canada, N1R 3G2
      • Novartis Investigative Site
    • Kingston, Ontario, Canada, K7L 5P9
      • Novartis Investigative Site
    • Kitchener, Ontario, Canada, N2G 1G3
      • Novartis Investigative Site
    • London, Ontario, Canada, N6A 5W9
      • Novartis Investigative Site
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Sault Ste Marie, Ontario, Canada, P6A 2C4
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4C 3E7
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5B 1W8
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M2K 1E1
      • Novartis Investigative Site
    • Windsor, Ontario, Canada, N8W 2X3
      • Novartis Investigative Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3T 1E2
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H4J 1C5
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3A 1A1
      • Novartis Investigative Site
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Novartis Investigative Site
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Canadian men, pre/postmenopausal women with advanced HR+ HER2- breast cancer and currently receiving endocrine therapy (ET) or ET plus targeted therapy (TT).

Description

INCLUSION CRITERIA:

1. Patient is an adult, male or female ≥ 18 years old at the time of informed consent.
2. Patient has histologically and/or cytologically confirmed diagnosis of breast cancer.
3. Patient has inoperable locally advanced or metastatic breast cancer.
4. Patient has ER positive and/or PgR positive HER2-negative breast cancer by local laboratory testing (based on most recently analyzed biopsy).

5. In the case of women, both pre/perimenopausal and postmenopausal patients are allowed to be included in this study.

   1. Postmenopausal status is defined as per investigator's judgment. Definition included as guidance only:

1. Prior bilateral oophorectomy 2. Or age ≥60 3. Or age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression), and FSH and estradiol in the postmenopausal range per local normal range. If patient is taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels should be in postmenopausal range per local normal range.

b) Premenopausal status is defined as per investigator's judgment. Definition included as guidance only:

1. Patient had last menstrual period within the last 12 months 2. Or if on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range 3. Or in case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.

c) Perimenopausal status is defined as neither premenopausal nor postmenopausal as per investigator's judgment.

6. Patient having received maximum one prior chemotherapy line for advanced/metastatic breast cancer is allowed.

Note: A chemotherapy line in advanced disease is an anticancer regimen(s) that contains at least 1 cytotoxic chemotherapy agent and given for 21 days or longer. If a cytotoxic chemotherapy regimen was discontinued for a reason other than disease progression and lasted less than 21 days, then this regimen does not count as a "prior line of chemotherapy".

7. Patient receiving targeted therapy plus endocrine therapy (ET+TT) in either the 1st, 2nd or 3rd line or endocrine therapy alone (ET) in either the 2nd or 3rd line advanced metastatic setting:

1. as per approved Health Canada indication OR
2. as per available expanded treatment protocol(s) only if efficacy assessments in these protocols are considered routine standard of care OR

3. as per available compassionate / expanded access program

   Notes: 1. Date of initiation of treatment should be a maximum of 12 months prior to the date of enrollment in this study for patients receiving CDK4/6 inhibitor therapy based combinations. Date of initiation of treatment should be a maximum of 1 month prior to the date of enrollment in this study for patients receiving all other endocrine monotherapies or combination therapies. 2. 1st, 2nd and 3rd line therapy in the advanced setting is defined as the first, second and third treatment received respectively in the metastatic setting (which could include endocrine monotherapy, targeted therapy combination with endocrine therapy or chemotherapy). 3. 3. Patients enrolled in the ET cohort must have received a prior CDK4/6 inhibitor for advanced/metastatic breast cancer. Patients who have received two subsequent lines of CDK4/6 inhibitor therapy are allowed.

   8. The decision to use ET or ET+TT has been reached prior to and independently of the current study.

   9. Patient willing to be followed according to routine standard of care practice.

   10. Signed informed consent to allow the collection of the data for the purposes of this study.

   EXCLUSION CRITERIA:

   1. Patient currently receiving chemotherapy at baseline/study entry is excluded (however patient could have received up to one line of chemotherapy in the metastatic setting prior to study entry or as a subsequent therapy after completion of ET or ET+TT treatment).
   2. Patient having received more than 3 lines of therapy in the metastatic setting.
   3. Any contraindications to the study treatments as presented in the respective Canadian Product Monographs for each therapy.
   4. Patient is participating in a clinical trial for an investigational treatment with the exception expanded treatment protocol or access program where efficacy assessments are considered routine standard of care.
   5. Patient is undergoing any treatment that is not considered standard of care as per regional policies and guidelines with the exception of treatments accessed via expanded treatment protocols or access programs.
   6. Patient does not understand or is not willing to sign the informed consent for participation in the study.
   7. According to the judgment of the physician participation in the study may interfere with the treatment or compromise the well-being of the patient.
   8. Patient is expected to travel for an extensive time period or be unavailable during the study period.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1: Endocrine Therapy (ET); HR+ HER2- male, female pre/postmenopausal advanced breast cancer patients being treated with endocrine therapy	Drug: Endocrine therapy may include one of the following therapies: letrozole, anastrozole, exemestane, tamoxifen or fulvestrant
Cohort 2: Endocrine Therapy (ET) plus Targeted Therapy (TT); HR+ HER2- male, female pre/ postmenopausal advanced breast cancer patients being treated with endocrine therapy in combination with targeted therapy including CDK4/6 inhibitor therapy	Drug: Endocrine therapy in combination with targeted therapy may include: everolimus plus exemestane or CDK4/6 inhibitor plus endocrine therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration on Treatment	To describe the duration on treatment with ET and ET+TT by cohort subgroups defined by (but not limited to) previous treatment with a CDK4/6 inhibitor plus endocrine therapy combination and according to the current line of treatment for advanced breast cancer up to and including 3rd line	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Sequencing	To describe the sequence of therapies and treatment patterns used for the management of advanced breast cancer.	Up to approximately 72 months
Monitoring Patterns	To characterize monitoring patterns associated with complete blood count (CBC), liver function tests (LFT), electrolytes and electrocardiogram (ECG) specifically in patients treated with CDK4/6-based combinations.	Up to approximately 72 months
Overall Survival (OS)	To describe the therapeutic effectiveness of endocrine therapy (ET) and ET in combination with targeted therapy (TT) as measured by OS.	Up to approximately 72 months
Health Care Resource Utilization (HCRU)	To describe HCRU related to management of advanced breast cancer.	Up to approximately 72 months
Health Related Quality of Life (HRQoL - EORTC QLQ-C30)	To describe the change in HRQoL EORTC 30 questionnaire QLQ-C30	Up to approximately 72 months
HRQoL BR23	To describe the change in HRQoL Breast Cancer 23 Questionnaire BR23	Up to approximately 72 months
Work-Related Productivity	To describe the change in work-related productivity.	Up to approximately 72 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2016
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: April 20, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: adult; targeted therapy; metastatic; men; prospective; registry; advanced breast cancer; observational; CDK; endocrine therapy; real world setting; non-interventional; Canadian; CRAD001; HR+ HER2; pre/postmenopausal; non steroidal aromatase inhibitor (NSAI) exposure; cyclin dependent kinase
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Fulvestrant; Tamoxifen; Everolimus; Anastrozole; Exemestane
• Other Study ID Numbers: CRAD001YCA09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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