A Real-world Study of Effectiveness and Safety in HR+/HER2- Breast Cancer Patients Treated With Ribociclib or Alpelisib

Real-world Effectiveness and Safety in HR+/HER2- Advanced or Metastatic BC Patients Treated With Ribociclib or Alpelisib: A European Non-interventional Retrospective Study (REASSURE)

This study was a multinational and multicenter cohort study of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer (aBC/mBC) treated with ribociclib or alpelisib between the period of 01 January 2018 and 30 September 2021. Patients who were receiving active treatment for malignancies other than BC or participating in a clinical trial were excluded. This study was conducted retrospectively with secondary use of data.

Study Overview

• Status: Completed
• Conditions: Hormone Receptor Positive HER-2 Negative Breast Cancer

• Study Type: Observational
• Enrollment (Actual): 435

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

This was a retrospective, noninterventional cohort study.

Description

Inclusion criteria:

• Confirmed diagnosis of locally advanced/metastatic not amenable to surgery HR+/HER2- BC (progressed following prior therapy or de novo) for whom the treating physician took the decision to initiate treatment with ribociclib or alpelisib.
• Patients with at least one prescription for ribociclib or alpelisib during the index period (01 January 2018 to 30 September 2021).

Exclusion criteria:

• Patients who were participating in any interventional clinical trial that included investigational or marketed products at the time of index (ribociclib, alpelisib, and other); patients who were participating in other investigator-initiated research or non-interventional study (NIS) could be included as long as their standard of care was not altered by the study.
• Patients on active treatment for malignancies other than HR+/HER2- aBC/mBC at the time of index.

• IPO-Porto cohort only:

  • Patients who had participated or were participating in any interventional clinical trial that included investigational or marketed products at the time of index (ribociclib, alpelisib, and others).
  • Patients who underwent part of the treatment for locally advanced/metastatic not amenable to surgery HR+/HER2- BC outside the center.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Institut de Cancérologie de l'Ouest (ICO) Cohort; Patients with HR+/HER2- advanced or metastatic BC who were registered in IQVIA's oncology evidence network (OEN), ICO, and initiated treatment with ribociclib or alpelisib.
L'Institut Curie (Curie) Cohort; Patients with HR+/HER2- advanced or metastatic BC who were registered in IQVIA's OEN, Curie, and initiated treatment with ribociclib or alpelisib.
Instituto Português de Oncologia do Porto (IPO-Porto) Cohort; Patients with HR+/HER2- advanced or metastatic BC who were registered in IQVIA's OEN, IPO-Porto, and initiated treatment with ribociclib or alpelisib.
Czech Republic Cohort; Patients with HR+/HER2- advanced or metastatic BC who were registered in Czech Republic local sites or clinics proposed by Novartis affiliates and initiated treatment with ribociclib or alpelisib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world Progression-free Survival (rwPFS)	rwPFS was defined as the time from the index date to the date of the first documented progression or death due to any cause. If a patient did not have an event, rwPFS was censored at the date of the last adequate tumor assessment. The index date was defined as the date of the first treatment with ribociclib or alpelisib.	Up to 51 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gender		Baseline
Age		Baseline
Body Mass Index (BMI)		Baseline
Number of Patients by Age Group	Age groups: Younger than 65 years; 65 years or older	Baseline
Number of Patients Categorized by Year of Index Date	The index date was defined as the date of the first treatment with ribociclib or alpelisib.	Baseline
Number of Patients With a History of Breast Cancer		Baseline
Number of Patients by Comorbidity	Comorbidities included: Diabetes mellitus; Cardiovascular disease; Cerebrovascular disease; Chronic obstructive pulmonary disease (COPD); Dementia; Depression; Heart Failure; Hypertension; Hypothyroidism; Ischemic heart disease; Liver disease; Myocardial infarction; Osteoporosis; Peripheral vascular disease; Renal Disease; Rheumatological disease; Ulcer disease; Other	Baseline
Number of Patients per BMI Category	BMI Categories: Underweight: below 18.5 kilograms per meter squared (kg/m^2); Healthy/normal weight: 18.5 to 24.9 kg/m^2; Pre-obesity: 25 to 29.9 kg/m^2; Obesity: 30 kg/m^2 and higher	Baseline
Number of Patients by Menopausal Status	Menopausal status: Pre- or peri-menopausal; Post-menopausal	Baseline
Number of patients per Charlson Comorbidity Index (CCI) Score Category	CCI predicts the ten-year mortality for a patient who may have a range of comorbid conditions. Comorbidity was assessed using the CCI, categorized as low (0-1) and high (≥2).	Baseline
Number of Patients Categorized by Duration of Disease Recurrence	Disease recurrence categories: 12 months or less; More than 12 months	Baseline
Number of Patients by Smoking Status	Smoking status: Current smoker; Former smoker; Never smoked	Baseline
Number of Patients Categorized by Primary Tumor Type	Tumor types: Invasive ductal; Lobular carcinoma; Other	Baseline
Number of Patients Categorized by Disease Site	Disease site categories: Non-visceral; Visceral; Multiple	Baseline
Number of Patients With Primary Metastatic Disease		Baseline
Number of Patients Categorized by Number of Metastatic Sites	Categories for number of metastatic sites: 0, 1, 2, 3, 4 or more.	Baseline
Number of Patients Categorized by Type of Metastases	Metastases: Local/breast metastases; Bone metastases; Lung metastases; Liver metastases; Central nervous system metastases; Lymph node metastases; Other metastases	Baseline
Number of Patients Categorized by Time From Diagnosis to Metastasis	Categories: 24 months or less; More than 24 months; Metastatic BC at diagnosis	Baseline
Number of Patients With Asymptomatic Disease		Baseline
Number of Patients Categorized by Tumor Grade	Tumor Grades: Grade 1; Grade 2; Grade 3	Baseline
Number of Patients Categorized by Stage of Cancer	Cancer Stages: I, IIA, IIB, IIIA, IIIB, IIIC, and IV.	Baseline
Number of Patients by Eastern Cooperative Oncology Group (ECOG) Performance Score	ECOG performance score describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). Scores ranged from a lower value of 0 (fully active, able to carry out all pre-disease performance without restriction) up to 4 (completely disabled; cannot carry out any selfcare; totally confined to bed or chair).	Baseline
Number of Patients Categorized by Previous Types of Treatment	Treatment categories: Chemotherapy; Surgery; Radiotherapy; Adjuvant endocrine therapy; Everolimus treatment	Baseline
Number of Patients Categorized by the Number of Prior Lines of Endocrine Therapy (ET)	Categories for number of lines of ET: 0, 1, 2, and 3 or more.	Baseline
Number of Patients Resistant to ET		Baseline
Number of Patients Sensitive to Hormonal Therapy		Baseline
Number of Patients Categorized by Line of Cyclin-dependent Kinase 4/6 Inhibitor (CDK4/6i) Treatment Received	CDK4/6i lines of treatment: Adjuvant; 1st metastatic line; 2nd metastatic line; 3rd metastatic line or later	Baseline
Number of Patients Categorized by the Number of Previous Lines of Treatment	Categories for number of lines of treatment: 0, 1, 2, and 3 or more.	Baseline
Baseline Neutrophil-to-lymphocyte Ratio (NLr)		Baseline
Baseline Platelet-to-lymphocyte Ratio (PLr)		Baseline
Baseline Lymphocytes-to-monocytes Ratio (LMr)		Baseline

Collaborators and Investigators

• Sponsor: Novartis
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2021
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Estimated): November 26, 2024

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: CLEE011A3002