Retrospective Study of 2nd-line Therapies After CDK4/6i + Hormonal Therapy in HR+/HER2- Advanced Breast Cancer

Study Overview
=================
Brief Summary
-----------------
Description of the choices for second line treatment, in the normal clinical practice of the centers adhering to the Hermione Network, in patients affected by advanced HR+/HER2- breast cancer who progressed after CDK4/6i in association with hormonal therapy.

Detailed Description
-----------------
Multicenter retrospective observational study, describing therapeutic choices as second-line treatment in patients with HR + / HER2- advanced breast cancer in a real world setting, in centers adhering to the Hermione Network. The study involves the analysis of patients with HR + / HER2- advanced breast cancer treated in second line after initial treatment failure with aromatase inhibitor or Fulvestrant + CDK4 / 6i (Palbociclib, Ribociclib or Abemaciclib). Data will be collected from 150 patients with at least one radiological re-evaluation of disease during 2nd-line treatment from 01 January 2016 until 31 December 2020. List of collected information: Patients' characteristics (gender, age at diagnosis, menopausal state); Disease definition at diagnosis (stage, tumour histology, hormonal status); Surgery (date of surgery, type of surgical approach); Neo-adjuvant treatment; Adjuvant treatment; Date of first relapse (and time since the end of adjuvant therapy); Locations of metastases, Biopsy of metastases, Hormonal receptor status; First-line treatment, hormonal therapy, Best response, Cause of treatment end; Second-line treatment, Best response (radiological re-evaluation), Toxicity, Cause of treatment end. Demographics, baseline characteristics (including tumor characteristics) and treatment information will be summarized descriptively. The categorical variables will be presented in the form of frequencies and percentages, while the continuous variables will be presented by mean, standard deviation and minimum and maximum values. A logistic model will be used for the analysis of clinical benefit (categorical variable), while for the analysis of time-to-event indicators a proportional hazard model will be used. For both analyses, the optimal model will be chosen with the method of backward selection. A threshold value of 5% will be used to include predictive variables in the model. The estimates derived by the final models will be evaluated using a penalized model for the evaluation of maximal probability, according to the Firth approach.

Official Title
-----------------
Multicenter Retrospective Observational (Descriptive) Study of Second-line Therapies After Progression to CDK4/6i in Association With Hormone Therapy, in Patients With HR+/HER2- Advanced Breast Cancer (HERMIONE 13)

Conditions
-----------------
Advanced Breast Cancer, Hormone Receptor Positive Breast Carcinoma, HER2-negative Breast Cancer

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age> 18 years female sex Performance Status (ECOG) 0-2; hormonal-receptor positive breast cancer (Estrogen and / or Progesterone positive), HER2 negative, with evidence of stage IV / locally advanced inoperable disease Radiologically documented progression in 1st line treatment with Hormonal Therapy (Aromatase inhibitor / Fulvestrant) + CDK4-6i (Palbociclib / Ribociclib / Abemaciclib) Execution of at least one subsequent therapeutic line chosen by the clinician, with at least one radiological re-evaluation during this treatment by 31 December 2020. Radiologically measurable or evaluable lesions Written informed consent Exclusion Criteria: age <18 years previous neoplastic pathology, within 5 years of the last active treatment Previous chemotherapy treatments, with biological or endocrine therapies for advanced disease, different from first-line therapy with OT + CDK4 / 6i

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the choices for second line treatment in patients affected by advanced HR+/HER2- breast cancer who progressed after CDK4/6i in association with hormonal therapy. | Description of the choices for second line treatment, in the normal clinical practice of the centers adhering to the Hermione Network, in patients affected by advanced HR+/HER2- breast cancer who progressed after CDK4/6i in association with hormonal therapy. | Entire study duration, approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | time from the start of treatment to evidence of disease progression or death | from date of treatment beginning until the date of first documented progression or date of death from any cause, assessed up to 72 months | 
| response rate | radiological response rate according to RECIST criteria, classified as CR (Complete Response), PR (Partial Response), SD (Stable Disease), PD (Progressive Disease) | Entire study duration, approximately 12 months | 
| Survival Post Progression | survival evaluated from from date of treatment beginning until the date of first documented progression or date of death from any cause | from date of treatment beginning until the date of first documented progression or date of death from any cause, assessed up to 72 months | 
| progression by location (visceral versus non-visceral). | time from the date second-line treatment beginning to the date of disease progression or death from any cause, stratified according to visceral versus non-visceral diseaes | from date of treatment beginning until the date of first documented progression or date of death from any cause, assessed up to 72 months | 
| Drug toxicities | Evaluation of drug related toxicities listed according to the different therapeutic options | Entire study duration, approximately 12 months | 
| Physician's reasons for treatment choice in real world experience | Evaluation of the physician's reasons for treatment choice of the second-line therapy after progression to CDK4 / 6i associated with hormonal therapy | Entire study duration, approximately 12 months | 
| Predictive factors of response | Evaluation of predictive factors of response through the comparison of four variables according to AIC e R2 criteria | Entire study duration, approximately 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
advanced breast cancer, hormonal therapy, CDK 4/6 inhibitors