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Completed

NCT Number: NCT07498413

Epidemiology and Treatment of HR+/HER2- Breast Cancer in England

The aim of this study was to describe the epidemiology, treatment pathway, treatment access, wastage of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), and health care resource use among adults with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer (BC) in England, including their treatment pathway leading to progression to metastatic BC for those who were initially diagnosed with early BC. This was a retrospective cohort study using linked registry and administrative data.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Disease Attributes Disease Progression Neoplasms Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Novartis

London, W12 7FQ, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patient with a registered diagnosis of International Classification of Diseases,10th Revision (ICD-10) code C50: malignant neoplasm of the breast, between 01 April 2012 and 31 December 2022.
  • Patient ≥18 years of age at diagnosis.
  • Patient with estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+), i.e., hormone receptor positive (HR+) breast cancer
  • Patient with human epidermal growth factor receptor 2 negative (HER2-) breast cancer.

Additional inclusion criteria for patients with metastatic BC were defined as:

  • Tumor stage IV at diagnosis or on subsequent treatment or
  • Tumor Node Metastases (TNM) staging indicative of M1 at diagnosis or on subsequent treatment or
  • Record with ICD-10 codes indicating secondary malignant neoplasm C77* (excluding C771 and C773), C78*, or C79* or
  • Initiation of treatment specified for metastatic BC, defined as ribociclib or palbociclib from 01 January 2017 to the end of the study period or abemaciclib from 01 January 2017 to 31 May 2022 or
  • Record of treatment for distant/metastatic recurrence.

An additional inclusion criterion for patients with early BC was:

  • No evidence of metastatic disease (defined above) before or up to 100 days after the first BC diagnosis date.

Additional inclusion criteria for patients in the NATALEE Trial-aligned sub-cohort:

  • Patient with stage IIa BC at diagnosis (i.e., T0-1 N1 or T2 N0 with Grade 3 tumor), or
  • Stage IIb BC at diagnosis (i.e., T2 N1, T3 N0), or
  • Stage III BC at diagnosis.

Exclusion criteria

  • Patient's sex unknown.
  • Patient with ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS).
  • Patient with a diagnosis of Second Edition of the International Classification of Diseases for Oncology (ICD-0-O2) code 0, 1, or 2 denoting non-malignant disease.
  • Patient with any indication of co-positive disease before or within 6 months after diagnosis (i.e., HR+ and HER2+) including:
  • treated with trastuzumab
  • treated with tyrosine kinase inhibitors (TKIs)
  • Any registered BC tumor or evidence of metastatic cancer prior to index date.

Treatment and study plan

Primary outcomes

  1. Time Between Start of Endocrine Therapy (ET) and Disease Progression

    Time frame: Up to approximately 12 years and 7 months

    Disease progression events include:

    • Return of breast cancer after initial treatment (non-metastatic recurrence)
    • Return and spread of breast cancer to other body parts after initial treatment (metastatic recurrence)
    • Death
    • Any other non-breast invasive cancer

  2. Time between Non-metastatic Recurrence and Disease Progression

    Time frame: Up to approximately 12 years and 7 months

    Disease progression events include:

    • Further non-metastatic recurrence
    • Metastatic recurrence
    • Death

  3. Time Between Metastatic Recurrence and Death

    Time frame: Up to approximately 12 years and 7 months

  4. Number of Patients With Disease Progression by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Start of ET to any other non-breast invasive cancer
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Further non-metastatic recurrence to death
    • Metastatic recurrence to death

  5. Invasive Disease-Free Survival (iDFS)

    Time frame: Up to approximately 12 years and 7 months

    iDFS was defined as time between start of ET to the first of any of non-metastatic recurrence, metastatic recurrence, non-breast invasive cancer, or death from any cause.

  6. Hazard Ratio for Disease Progression Between Health States

    Time frame: Up to approximately 12 years and 7 months

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Further non-metastatic recurrence to death
    • Metastatic recurrence to death

  7. Number of Patients by Number of Lines of Systemic Anti-cancer Therapy (SACT) Received

    Time frame: Up to approximately 12 years and 7 months

  8. Number of Patients who Received Radiotherapy

    Time frame: Up to approximately 12 years and 7 months

  9. Time From BC diagnosis to Treatment Initiation by Line of Therapy (LOT)

    Time frame: Up to approximately 12 years and 7 months

  10. Number of Patients by Treatment Received Within Each LOT Ranked by Frequency of Use

    Time frame: Up to approximately 12 years and 7 months

    Treatments were ranked by most common (rank 1) to least common (rank 3).

  11. Duration of Treatment Received for Each LOT by Rank Order

    Time frame: Up to approximately 12 years and 7 months

    Treatments were ranked by most common (rank 1) to least common (rank 3).

  12. Number of Patients by Treatment Classes per LOT

    Time frame: Up to approximately 12 years and 7 months

  13. Percentage of Patients by First SACT Used During Year of Diagnosis by Geographical Region

    Time frame: Up to approximately 1 year

  14. Number of Patients Diagnosed With Early BC and Metastatic BC by Year of Diagnosis

    Time frame: 3 years

  15. Number of Patients Diagnosed with Early BC and Metastatic BC by Geographical Region

    Time frame: 3 years

  16. Number of Metastatic BC Patients by First-line Chemotherapy and Age Group

    Time frame: Up to approximately 7 years and 10 months

    Treatments were categorized as anthracycline with taxane, anthracycline without taxane, taxane without anthracycline, CDK4/6i, and other.

  17. Number of Metastatic BC Patients by First-line Chemotherapy and Ethnicity

    Time frame: Up to approximately 7 years and 10 months

    Treatments were categorized as anthracycline with taxane, anthracycline without taxane, taxane without anthracycline, CDK4/6i, and other.

  18. Number of Metastatic BC Patients by First-line Chemotherapy and Deprivation Quintile

    Time frame: Up to approximately 7 years and 10 months

    Deprivation quintiles ranged from 1 (least deprived) to 5 (most deprived). Treatments were categorized as anthracycline with taxane, anthracycline without taxane, taxane without anthracycline, CDK4/6i, and other.

Secondary outcomes

  1. Number of Patients by Demographic Category

    Time frame: Baseline

    Demographics included:

    • Age
    • Gender
    • Ethnicity
    • Deprivation quintiles (1 [least deprived] to 5 [most deprived])

  2. Number of Patients by Clinical Characteristic Category

    Time frame: Baseline

    Clinical characteristics include:

    • Charlson comorbidity index (CCI) score
    • Tumor stage
    • Eastern Cooperative Oncology Group (ECOG) performance status score
    • Comorbidities

  3. Time From First Early BC Diagnosis to Metastatic BC Diagnosis

    Time frame: Up to approximately 10 years and 7 months

  4. Number of Early BC Patients who Discontinued Treatment Within 6 Months of Treatment Initiation

    Time frame: 6 months

  5. Number of Early BC Patients by Reason for Discontinuing Treatment Within 6 Months of Treatment Initiation

    Time frame: 6 months

  6. Number of Patients Adherent to Treatment Among Early BC Patients who Progressed to Metastatic BC

    Time frame: Up to approximately 12 years and 7 months

    Patients were considered adherent when the number of completed treatment cycles was greater than or equal to the number of planned treatment cycles per patient.

  7. Number of Patients With Metastatic BC Treated With a CDK4/6i

    Time frame: Up to approximately 7 years and 10 months

    CDK4/6is included ribociclib, palbociclib and abemaciclib.

  8. Time From Metastatic BC Diagnosis to Initiation of CDK4/6i Treatment

    Time frame: Up to approximately 7 years and 10 months

    CDK4/6is included ribociclib, palbociclib and abemaciclib.

  9. Duration of CDK4/6i Treatment Among Patients With Metastatic BC

    Time frame: Up to approximately 7 years and 10 months

    CDK4/6is included ribociclib, palbociclib and abemaciclib.

  10. Number of Patients With Metastatic BC Treated With a CDK4/6i who Received Electrocardiograms (ECGs) Outside of Standard of Care Recommendations

    Time frame: Up to approximately 7 years and 10 months

    CDK4/6is included ribociclib, palbociclib and abemaciclib.

  11. Hazard Ratio for Factors Associated With Progression Free Survival (PFS) Among Patients With HR+/HER2- BC

    Time frame: Up to approximately 12 years and 7 months

    Factors included age group, ethnicity, deprivation quintile, geographical region, and first LOT.

    PFS for early BC patients was defined as the time from date of first breast surgery (or diagnosis if no surgery) until the earliest of: new surgical procedures (breast surgery); change in category A SACT treatment or new radiotherapy at least 3 months after initial surgery (or diagnosis if no surgery); non-metastatic recurrence, metastatic recurrence, death.

    PFS for metastatic BC patients was defined as the time from date of diagnosis with metastatic BC until the earliest of: change in category A SACT treatment or new radiotherapy at least 3 months after diagnosis with metastatic BC; a new metastasis record after diagnosis with metastatic BC; death.

    Category A treatment classes were categorized as anthracycline without taxane, taxane without anthracycline, anthracycline with taxane, CDK4/6i, and other.

  12. Odds Ratio for Factors Associated With Timeliness of Initiating Treatment Following Metastatic BC Diagnosis

    Time frame: Up to approximately 12 years and 7 months

    Factors included age group, ethnicity, deprivation quintile, and geographical region. Timeliness of treatment was defined as having received treatment within 31 days of decision to treat for metastatic BC diagnosis.

  13. Odds Ratio for Factors Associated With Metastatic Status at First Presentation

    Time frame: Up to approximately 12 years and 7 months

    Factors included age group, ethnicity, deprivation quintile, and geographical region. Metastatic status at first presentation was defined as de novo or progressed metastatic disease.

  14. Number of Metastatic BC Patients Treated With a CDK4/6i by Number of Dose Reductions Experienced

    Time frame: Up to approximately 7 years and 10 months

    CDK4/6is included ribociclib, palbociclib, or abemaciclib.

  15. Length of CDK4/6i Treatment for Patients With Metastatic BC by Number of Dose Reductions

    Time frame: Up to approximately 7 years and 10 months

    CDK4/6is included ribociclib, palbociclib, or abemaciclib.

  16. Number of CDK4/6i Treatment Cycles Received Before a Dose Reduction

    Time frame: Up to approximately 7 years and 10 months

    CDK4/6is included ribociclib, palbociclib, or abemaciclib. A treatment cycle is 28 days.

  17. Cost Associated With CDK4/6i Wastage due to Dose Reduction

    Time frame: Up to approximately 7 years and 10 months

    CDK4/6is included ribociclib, palbociclib, or abemaciclib.

  18. Number of Metastatic BC Patients who Switched CDK4/6i Categorized by the Treatment Patients Switched From and To

    Time frame: Up to approximately 7 years and 10 months

    CDK4/6is included ribociclib, palbociclib, or abemaciclib.

  19. Number of Patients by All-cause Healthcare Admission and Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Healthcare admissions included inpatient admissions, outpatient appointments, and emergency care visits.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  20. Number of All-cause Healthcare Admissions per Patient per Month (PPPM) by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Healthcare admissions included inpatient admissions, outpatient appointments, and emergency care visits.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  21. Number of BC-related Healthcare Admissions PPPM by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    BC-related healthcare admissions included inpatient admissions and outpatient appointments.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  22. Number of Inpatient Bed Days PPPM by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  23. Number of Patients by Toxicity-related Inpatient Admission and Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Toxicity-related admissions were defined as those with a record of a chemotherapy side effect, including but not limited to neutropenic sepsis, cardiotoxicity and arrhythmia, diarrhea and vomiting causing dehydration requiring admission to hospital, and fragility fractures.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  24. Number of Patients by Toxicity-related Outpatient Appointment and Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Toxicity-related care was defined as an outpatient appointment with a specialty that corresponds to the specified toxicity, including but not limited to cardiology, gastroenterology, and rheumatology or orthopedic surgery.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  25. Number of Toxicity-related Inpatient Admissions PPPM by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Toxicity-related admissions were defined as those with a record of a chemotherapy side effect, including but not limited to neutropenic sepsis, cardiotoxicity and arrhythmia, diarrhea and vomiting causing dehydration requiring admission to hospital, and fragility fractures.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  26. Number of Toxicity-related Outpatient Appointments PPPM by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Toxicity-related care was defined as an outpatient appointment with a specialty that corresponds to the specified toxicity, including but not limited to cardiology, gastroenterology, and rheumatology or orthopedic surgery.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  27. Median Cost PPPM of All-cause Healthcare Admissions by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Healthcare admissions included inpatient admissions, outpatient appointments, and emergency care visits.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  28. Median Cost PPPM of BC-related Healthcare Admissions by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    BC-related healthcare admissions included inpatient admissions and outpatient appointments.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  29. Median Cost PPPM of Toxicity-related Inpatient Admissions by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Toxicity-related admissions were defined as those with a record of a chemotherapy side effect, including but not limited to neutropenic sepsis, cardiotoxicity and arrhythmia, diarrhea and vomiting causing dehydration requiring admission to hospital, and fragility fractures.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

  30. Median Cost PPPM of Toxicity-related Outpatient Appointments by Health State Transition

    Time frame: Up to approximately 12 years and 7 months

    Toxicity-related care was defined as an outpatient appointment with a specialty that corresponds to the specified toxicity, including but not limited to cardiology, gastroenterology, and rheumatology or orthopedic surgery.

    Health states:

    • Start of ET to non-metastatic recurrence
    • Start of ET to metastatic recurrence
    • Start of ET to death
    • Non-metastatic recurrence to further non-metastatic recurrence
    • Non-metastatic recurrence to metastatic recurrence
    • Non-metastatic recurrence to death
    • Metastatic recurrence to death

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Acronym: ROTOR

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Mar 27, 2026
Registry last updated
Apr 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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