First-line Palbociclib and Endocrine Therapy for Patients With HR+/HER2- Advanced Breast Cancer in the Real-world Setting.

Study Overview
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Brief Summary
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This is a prospective, single-arm, multi-center observational non-interventional study (NIS) in Germany and Austria.

Detailed Description
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Patients diagnosed with HR+/HER2- locally advanced or metastatic breast cancer indicated by their treating physicians for first line endocrine-based palbociclib combination therapy and who meet eligibility criteria will be invited to participate in this study. The key objectives of this study are to describe clinical, scientific and patient reported outcomes for patients with HR+/HER2- locally advanced or metastatic breast cancer initiating treatment with first line endocrine-based palbociclib combination therapy in the real-world setting in Germany and Austria. Patient characteristics, real-world treatment patterns, treatment sequences and reasons for the physician's treatment decisions will be collected. Additional real-world research questions are to explore patient-focused parameters such as longitudinal follow-up data on patient-reported outcomes beyond disease progression and by treatment sequence or to analyze the time from the start of first line treatment to the first administered palliative chemotherapy. Clinical outcome by treatment sequences will be described. Routinely assessed biomarkers and diagnostic procedures applied for treatment sequence decisions will be collected.

Official Title
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PERFORM: An EPidEmiological, PRospective Cohort Study to Generate Real-world Evidence in Patients With HR+/HER2- Advanced Breast Cancer Treated in the First Line Setting as Per Current Standard Of Care With an EndocRine-based Palbociclib CoMbination Therapy

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Palbociclib + endocrine therapy


Participation Criteria
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Eligibility Criteria
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Patients must meet all of the following inclusion criteria to be eligible for inclusion in the study: Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study. Diagnosis of HR+/HER2- locally advanced, inoperable or metastatic breast cancer. Physician has determined that first-line treatment with palbociclib (i) in combination with an aromatase inhibitor, or (ii) in combination with fulvestrant in women who received prior endocrine therapy as per current local product label is indicated. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Patients who in the opinion of the investigator are willing and able to comply with regular clinic visits as per local standard of care practice at the study site. Age of 18 years or older. Patients meeting any of the following criteria will not be included in the study: Any contraindication as per current local product label. Prior systemic antineoplastic treatment for advanced disease. Exception: Start of first line treatment with palbociclib in combination with aromatase inhibitor or fulvestrant as per current local product label is allowed up to 4 weeks prior to inclusion. Patients currently participating in any interventional clinical trial that includes investigational or marketed products at the time of enrollment. Note: A concomitant participation in other non-interventional/observational studies, registries and translational research networks (e.g., PRAEGNANT, OPAL) or chart reviews is allowed. Patients who are unable to understand the nature of the study or are unwilling to sign an informed consent. Patient eligibility should be reviewed, documented, and confirmed by an appropriately qualified member of the investigator's study team before patients are enrolled in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| First-line Palbociclib + endocrine therapy<br>Palbociclib + letrozole, or Palbociclib + anastrozole, or Palbociclib + exemestane, or Palbociclib + fulvestrant after prior endocrine therapy | Drug: Palbociclib + endocrine therapy<br>* Palbociclib + letrozole, or Palbociclib + anastrozole, or Palbociclib + exemestane, or Palbociclib + fulvestrant after prior endocrine therapy In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone-releasing hormone (LHRH) agonist.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | from date of start of first-line treatment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 7.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort-specific PFS of second-line treatment | Cohorts are defined by substance class of second-line therapy following first-line endocrine-based palbociclib therapy | from date of start of second-line treatment until the date of first subsequent documented disease progression or date of death from any cause, whichever came first, assessed up to 7.5 years | 
| Cohort-specific PFS2 |  | from date of start of first-line treatment until the date of documented disease progression on the respective second-line treatment or date of death from any cause, whichever came first, assessed up to 7.5 years | 
| Landmark progression-free survival rates (PFSR) of first- and second-line treatment |  | proportion of patients without documented disease progression or death due to any cause at defined intervals after start of first-/second-line treatment (at 6, 12, 18, 24, 30, 36 months) | 
| Overall survival (OS) |  | from date of start of first-line treatment until the date of documented death from any cause, assessed up to 7.5 years | 
| Landmark overall survival rates (OSR) |  | proportion of patients without documented death due to any cause at defined intervals (at 12, 24, 36, 48, 60 months after start of first-line treatment) | 
| Objective response rate (ORR) of first- and second-line treatment |  | from date of start of first-/ second-line treatment until the date of first subsequent documented disease progression or date of death from any cause, whichever came first, assessed up to 7.5 years | 
| Duration of response (DoR) of first- and second-line treatment |  | from the date of first documented tumor response during first-/ second-line treatment until to the date of first subsequent documented disease progression or to death due to any cause, whichever came first, assessed up to 7.5 years | 
| Disease control rate (DCR) of first- and second-line treatment |  | proportion of patients with documented tumor response during first-/second-line treatment (as assessed by local investigator in routine clinical practice) or stable disease (SD) over a period of at least 24 weeks after start of first-line treatment | 
| Progression-free survival (PFS) of third-line treatment |  | from date of start of third-line treatment until the date of first subsequent documented disease progression or date of death from any cause, whichever came first, assessed up to 7.5 years | 
| Time to first subsequent therapy (TFST) |  | from date of start of first-line treatment until the date of start of first subsequent systemic antineoplastic treatment, assessed up to 7.5 years | 
| Time to first subsequent chemotherapy (TFSC) |  | from date of start of first-line treatment until the date of start of first subsequent systemic chemotherapy or chemotherapy-based antineoplastic treatment, assessed up to 7.5 years | 
| Change from baseline in the FACT-B total score | The FACT-B is a 37-item instrument designed to measure five domains of Health-Relaed Quality of Life (HRQOL) in breast cancer patients: Physical Well-being (PWB), Social/family Well-being (SWB), Emotional Well-being (EWB), Functional Well-being (FWB) as well as a Breast Cancer Subscale (BCS). Utilized with the 27 core FACT-G items, the FACT-B was developed with an emphasis on patients' values and brevity. For all questions, participants are asked to respond to a 5-point Likert-type scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. The higher the score, the better the QOL (minimum 0; maximum 148). | from the date of first questionnaire assessment until the date of last questionnaire assessment, assessed at baseline, thereafter 3-monthly until end of study, and at the end of palbociclib treatment, up to 7.5 years. | 
| Change from baseline in the FACT-G total score | The FACT-G is a 27-item instrument designed to measure four domains of HRQOL in breast cancer patients: PWB, SWB, EWB, and FWB. For all questions, participants are asked to respond to a 5-point Likert-type scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. The higher the score, the better the QOL (minimum 0; maximum 108). | from the date of first questionnaire assessment until the date of last questionnaire assessment, assessed at baseline, thereafter 3-monthly until end of study, and at the end of palbociclib treatment, up to 7.5 years. | 
| Change from baseline in the FACT-B subscales scores: PWB, SWB, EWB, FWB and additional concerns for BCS. | The FACT-B is a 37-item instrument designed to measure five domains of HRQOL in breast cancer patients: PWB, SWB, EWB, FWB as well as a BCS. Utilized with the 27 core FACT-G items, the FACT-B was developed with an emphasis on patients' values and brevity. For all questions, participants are asked to respond to a 5-point Likert-type scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. The higher the score, the better the QOL (PWB: minimum 0; maximum 28. SWB: minimum 0; maximum 28. EWB: minimum 0; maximum 24. FWB: minimum 0; maximum 28. BCS: minimum 0; maximum 40). | from the date of first questionnaire assessment until the date of last questionnaire assessment, assessed at baseline, thereafter 3-monthly until end of study, and at the end of palbociclib treatment, up to 7.5 years. | 
| Change from baseline in FACT-B Trial Outcome Index (TOI) | The FACT-B is a 37-item instrument designed to measure five domains of HRQOL in breast cancer patients: PWB, SWB, EWB, FWB as well as a BCS. Utilized with the 27 core FACT-G items, the FACT-B was developed with an emphasis on patients' values and brevity. The TOI combines the PWB+FWB+BCS items, making it 24-items altogether. For all questions, participants are asked to respond to a 5-point Likert-type scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. The higher the score, the better the QOL (minimum 0; maximum 96). | from the date of first questionnaire assessment until the date of last questionnaire assessment, assessed at baseline, thereafter 3-monthly until end of study, and at the end of palbociclib treatment, up to 7.5 years. | 
| Time to deterioration (TTD) in FACT-B total score | The FACT-B is a 37-item instrument designed to measure five domains of HRQOL in breast cancer patients: PWB, SWB, EWB, FWB as well as a BCS. Utilized with the 27 core FACT-G items, the FACT-B was developed with an emphasis on patients' values and brevity. For all questions, participants are asked to respond to a 5-point Likert-type scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. The higher the score, the better the QOL (minimum 0; maximum 148). | From the date of first questionnaire assessment until the date of first subsequent questionnaire with a decrease of ≥ 7 points in FACT-B total score or death, whichever came first, assessed up to 7.5 years. | 
| Landmark analyses of cohort-specific Area Under the Curve (AUC) in the Functional Assessment of Cancer Therapy - Breast (FACT-B) TOI-Physical/Functional/Breast (TOI-PFB) | Cohorts are defined by substance class of second-line therapy following first-line endocrine-based palbociclib therapy. | From the date of first questionnaire assessment until 12, 24, 36, 48 months thereafter (irrespective of disease or treatment situation at that time point) |