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Predicting clinicAL outcoMes During First-line CDK4/6 Inhibitors Plus Endocrine Therapy in Patients With Advanced Hormone REceptor-poSitive HER2-negative Breast Cancer: the Retrospective-prospective Multicenter Italian PALMARES-2 Study

Predicting clinicAL outcoMes During First-line CDK4/6 Inhibitors Plus Endocrine Therapy in Patients With Advanced Hormone REceptor-poSitive HER2-negative Breast Cancer: the Retrospective-prospective Multicenter Italian PALMARES-2 Study

Recruiting
18 years and older
All
Phase N/A

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Overview

PALMARES-2 is a retrospective/prospective, observational, multicenter, population-based study, aiming at providing real-world evidences on HR+/HER2- aBC patients treated with first-line CDK4/6i plus ET. The present study has the objective to collect data coming from different sources, i.e. RWD, medical images and biological samples, from patients treated with CDK4/6i as first-line of therapy for HR+/HER2- aBC. In consideration of the complexity of data collected and different objectives of the study, this master protocol foresees different sub-studies, which encompasses different methodologies for data collection, data extraction and analyses.

Description

The PALMARES-2 study aims to collect data from different sources, i.e. real-world clinical data, medical images and biological data and samples, from patients treated with CDK4/6i as first-line therapy for patients with HR+/HER2- advanced breast cancer. Due to the complexity of the data collected and the different objectives of the study, this protocol includes several sub-studies, which include different methodologies for data collection, extraction and analysis:

  • The first sub-study (RWD sub-study) will aim to collect real-world clinical data of patients who received ET+CDK4/6i in the first-line setting; the primary objective of this sub-study is to assess whether there is a difference in OS between the three CDK4/6i in the real-world population, while secondary objectives include comparisons in specific sub-groups;
  • The second sub-study (Safety sub-study) includes the collection of comorbidities, concomitant medications and toxicities of patients enrolled in the study; the primary objective of this sub-study is to evaluate the difference in severe toxicity between the three CDK4/6i in the real-world population
  • The third sub-study (medical imaging sub-study) consists of the collection of computed tomography (CT) and fluorodeoxyglucose positron emission tomography (FdG-PET) images at baseline and digitised haematoxylin-eosin (HE) slides to build a multi-omics predictive model;
  • The fourth sub-study (translational sub-study) aims to collect tumour samples from a proportion of patients enrolled in the study to perform genomics and transcriptomics analyses; information from this data source will be integrated into the model built with the previous data to further improve the performance of the previous model
  • The fifth sub-study (subsequent lines sub-study) focuses on the lines of treatment administered to patients enrolled in the study at the time of progression after first-line treatment with ET+CDK4/6i, with the aim of building predictive models of response to subsequent lines of treatment, capable of supporting oncologists' and patients' decisions in this context.

Eligibility

Inclusion Criteria:

  • Diagnosis of HR+/HER2- advanced Breast Cancer (aBC), as defined as at least 1% estrogen receptor (ER) and/or progesterone receptor (PgR) positivity at IHC. HER2 negativity is defined on the basis of an IHC score of 0, 1+, or 2+ with absence of gene amplification at in situ hybridization (ISH) analyses.
  • Have received or are candidate to receive treatment with palbociclib, ribociclib or abemaciclib in combination with endocrine therapy as first-line treatment for HR+/HER2- aBC.

Exclusion Criteria:

  • Less than 3 months of follow up from the CDK4/6i start to the date of data cut-off;
  • Have received CDK4/6i as monotherapy;
  • Have received CDK4/6i as adjuvant treatment for localized disease.

Study details
    Breast Adenocarcinoma
    Breast Cancer Stage IV
    Breast Cancer
    Metastatic
    Breast Carcinoma
    Breast Diseases
    Breast Neoplasms
    Breast Neoplasms
    Male
    Breast Cancer
    Breast Cancer With Metastatic Bone Disease
    Breast Cancers
    Breast Neoplasm
    Breast Tumors
    HR+ HER2- Men
    Pre/Postmenopausal Advanced Breast Cancer
    HR+ Advanced or Metastatic Breast Cancer
    HR+/HER2- Breast Cancer
    HRpos Breast Neoplasms
    HR-positive
    HER2-negative Advanced Breast Cancer
    HR-positive
    HER2-negative and PIK3CA Mutation Advanced Breast Cancer
    HR-positive Breast Cancer
    Hormone Receptor-Positive Breast Cancer
    Hormone Receptor Positive Breast Adenocarcinoma
    Hormone Receptor Positive Breast Carcinoma
    Hormone Receptor Positive Breast Neoplasms
    Hormone Receptor Positive HER-2 Negative Breast Cancer
    Hormone Receptor Positive Malignant Neoplasm of Breast
    Hormone Receptor Positive Metastatic Breast Cancer
    Hormone Receptor Positive
    HER2 Negative Breast Cancer
    Hormone Receptor Negative Breast Cancer
    Hormone Receptor Positive
    HER2-negative
    Advanced Breast Cancer
    Hormone Receptor Positive Breast Cancer
    Hormone Receptor Positive (ER+/PR+
    and Her2-) Metastatic Breast Cancer
    Hormone Receptor Positive
    HER2-negative Neoplasms
    Hormone Receptor Positive
    HER2-low Neoplasms
    Hormone Receptor Positive (HR+)
    HER2-negative Breast Cancer
    Hormone Receptor (HR)-Positive Breast Cancer
    Hormone Receptor-Positive
    HER2-Negative Metastatic Breast Cancer
    Palbociclib
    Ribociclib
    Abemaciclib
    CDK4/6 Inhibitor
    CDK4/6 Inhibitors

NCT06805812

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

15 October 2025

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