A Non-interventional Study for Women With HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer to Evaluate the Real-world Effectiveness of Treatment Algorithms Beginning With Ribociclib + AI/FUL, or With Endocrine Therapy or Chemotherapy as First Line Treatment

Active, not recruiting

• Conditions: Breast Cancer
• Interventions: Drug: First-line Ribociclib + endocrine therapy; Drug: First-line endocrine therapy; Drug: First-line chemtherapy

• Registration Number: NCT06311383
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This is a non-interventional observational study conducted in Germany to evaluate the real-world effectiveness, tolerability, safety, and quality of life in patients with locally advanced/metastatic HR+/HER2- breast cancer treated with one of the following 1st line treatments: Ribociclib + AI/FUL, or endocrine monotherapy, or chemotherapy

Detailed Description

This non-interventional study collects data from clinical practice capturing on effectiveness, safety and tolerability, duration of therapy, and quality of life of ribociclib in combination with an aromatase inhibitor/fulvestrant in daily routine and in line with the respective current German summary of product characteristics. In order to put these results into perspective, data is also collected on patients treated with endocrine therapy or chemotherapy for first line locally advanced or metastatic breast cancer. To gain insight into algorithms and outcome of sequential therapy, up to three lines of treatment are documented within this study. The information gathered and evaluated in this NIS is helping to answer open questions for the treatment of locally advanced/metastatic breast cancer and provides first insights into the treatment reality with ribociclib in this setting. This includes, but is not limited to, the questions on baseline demographics leading to a specific treatment decision, as well as efficacy and clinical routine related to treatment sequencing. In addition, data on the mutation status (including PIK3CA and BRCA1/2) is collected at different time points to generate insights into the clinical routine of mutation testing and to understand its impact on therapy sequencing.

Study Timeline

• Study Start: 2017-10-09
• Study First Submitted: 2023-12-29
• Study First Submitted QC: 2024-03-13
• Study First Posted: 2024-03-15
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-04
• Last Update Posted: 2024-07-08
• Primary Completion: 2025-02-16
• Study Completion: 2025-02-16

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 2610

Inclusion Criteria

• Patients with a histological diagnosis of locally advanced/metastatic HR+/HER2- breast cancer. Histological diagnosis does not necessarily origin from metastasis, but must reflect the most recent disease status
• No prior systemic treatment for locally advanced/metastatic disease in the palliative setting
• The treating physician has made the decision to treat the patient
• with ribociclib in combination with an aromatase inhibitor or fulvestrant as initial treatment in first line, or
• endocrine therapy as initial treatment in first line (e.g. letrozole, anastrozole, fulvestrant), or
• chemotherapy as initial treatment in first line (e.g. taxanes, capecitabine, with or without bevacizumab)
• Written informed consent of the patient
• Patient who initiated treatment for first line no longer than 4 weeks (28 days) prior to written informed consent for this study
• Planned treatment is in line with the respective current German SmPC ("Summary of product characteristics")
• Patient is ≥18 years

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Exclusion Criteria

• Patients unable to provide written informed consent
• Contra-indication according to the respective current German SmPC ("Summary of product characteristics"), as judged by the treating physician
• The patient is currently under active treatment in an investigational study

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
First-line Ribociclib + endocrine therapy	First-line Ribociclib + endocrine therapy	Ribociclib + letrozole, or Ribociclib + anastrozole, or Ribociclib + exemestane, or Ribociclib + fulvestrant
First-line endocrine therapy	First-line endocrine therapy	As of physicians choice
First-line chemotherapy	First-line chemtherapy	As of physicians choice

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	Up to 88 months	Progression-free survival was defined as first intake of study medication in current-line therapy up to first documented progress or death from any cause in this treatment line. If a patient had not had an event, progression-free survival was censored at the end of the respective therapy line.

Secondary Outcome Measures

Name	Time	Method
Propensity Score matching for progression free survival in 1st line therapy	Up to 88 months	Propensity score matching (PSM) was performed to compare outcome between cohorts and performed separately for the Ribociclib+AI/FU vs. Chemotherapy cohort resp. the Ribociclib+AI/FU vs. Endocrine therapy cohort in a 5:1 ratio.
Dose reduction	Up to 88 months	Dose reduction rates and reasons
Time to treatment failure (TTF)	Up to 88 months	Time to treatment failure (TTF) from current-line therapy was defined as time between first intake of study medication in current-line therapy up to therapy discontinuation because of progress, adverse events leading to discontinuation or death.
Time to next treatment / therapy (TTNT) after 1st line treatment	Up to 88 months	Time to next treatment / therapy (TTNT) was defined as time between first intake of study medication in first-line therapy up to first intake of medication in the next therapy line.
Time to first chemotherapy	Up to 88 months	Time to first chemotherapy was defined as time between first intake of study medication in first-line therapy up to first application of chemotherapy for patients enrolled in 1st line option ribociclib + AI/FU or endocrine therapy.
Number of participants with mutations	Up to 88 months	Number of participants with mutations will be collected
Quality of life for specific cohorts and treatment lines - EORTC QLQ-B23	Up to 88 months	Quality of life during documented therapy lines was assessed using the EORTC QLQ-C30. Scale and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Sequential progression-free survival (PFS_S)	Up to 88 months	Sequential progression-free survival up to second-line therapy was defined as time between first intake of study medication in first-line therapy up to progress or death after second-line therapy. Sequential progression-free survival up to third-line therapy was defined as time between first intake of study medication in first-line therapy up to progress or death after third-line therapy. Sequential progression-free survival for all further therapy lines were analyzed according to the definitions above.
Conditional progression-free survival	Up to 88 months	Conditional progression-free survival in first-line therapy was defined as PFS for patients with a period of up to 6, 12, or 24 months from start of study treatment (first intake) up to first progression.; This means that all patients with progression or death within the first 24 months of first-line therapy are classified into one of the three subgroups: Progression in month 0 to 6, Progression in month 7 to 12 and Progression in month 13 to 24. For these subgroups, the PFS is presented separately.
Discontinuations	Up to 88 months	Discontinuations rates and reasons
Cox proportional hazard regression for progression free survival in 1st line therapy	Up to 88 months	Cox proportional hazard regression were calculated with the covariates treatment cohort, age group, previous therapy, ECOG performance status, grading status and metastasis status for the full analysis set excluding patients with missing data in covariates.
Overall survival (OS)	Up to 88 months	Overall survival (OS) was defined as time between first intake of study medication in first-line therapy up to death from any cause. If a patient was not known to have died, survival was censored at the date of last contact.
Dose interruption	Up to 88 months	Dose interruption rates and reasons
Adherence - MMAS-8 questionnaire	Up to 87 weeks	Patient adherence for ribociclib was assessed using the MMAS-8 questionnaire. This questionnaire was only send to patients enrolled in the first-line option ribociclib + AI/FU. The score was analyzed using descriptive statistics and adherence categories low, medium and high were displayed by visit. Questionnaires were only included if all questionnaire items were answered.; The total scale has a range of 0 to 8.0 where: * Low Adherence (\< 6); * Medium Adherence (6 to \<8); * High Adherence (= 8)
Quality of life for specific cohorts and treatment lines - EORTC QLQ-C30	Up to 88 months	Quality of life during documented therapy lines was assessed using the EORTC QLQ-C30. Scale and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Quality of life for specific cohorts and treatment lines - HADS-D	Up to 88 months	Quality of life during documented therapy lines was assessed using the HADS-D. Scale ranges between 0 and 21, a high score means a high level of anxiety or depression.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇩🇪 Wuerzburg, Germany