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

• Conditions: 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

• Registration Number: NCT06805812
• Lead Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2023-05-01
• Status Verified: 2024-12
• Study First Submitted: 2025-01-07
• Study First Submitted QC: 2025-01-28
• Last Update Submitted: 2025-01-28
• Study First Posted: 2025-02-03
• Last Update Posted: 2025-02-03
• Primary Completion: 2030-12-31
• Study Completion: 2040-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3500

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From the first-line treatment start to date of any-cause death or last follow up, up to 120 months

Secondary Outcome Measures

Name	Time	Method
Real-world Progression-Free Survival (rwPFS)	From the start of first-line treatment to date of disease progression documented in patient medical charts or death or last follow up, whichever occurs first, up to 120 months
Time To Next Treatment or Death (TTNT-D)	From the start of first-line treatment to date of subsequent therapy start or death or last follow up, whichever occurs first, up to 120 months
Time To Chemotherapy or Death (TTC-D)	From the start of first-line treatment to date of first chemotherapy for advanced disease start or death or last follow up, whichever occurs first, up to 120 months

Trial Locations

Locations (24)

ASST Lariana - Ospedale Sant'Anna; 🇮🇹 Como, Italy

ASST Ospedale Maggiore; 🇮🇹 Cremona, Italy

Azienda Ospedaliero Universitaria Careggi; 🇮🇹 Firenze, Italy

Ospedale San Martino; 🇮🇹 Genova, Italy

Istituto Tumori della Romagna IRST IRCCS; 🇮🇹 Meldola, Italy

Centro di Riferimento Oncologico IRCCS; 🇮🇹 Aviano, Italy

Azienda Socio Sanitaria Territoriale degli Spedali Civili; 🇮🇹 Brescia, Italy

Humanitas Istituto Clinico Catanese; 🇮🇹 Catania, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore; 🇮🇹 Milano, Italy

IEO Istituto Europeo di Oncologia; 🇮🇹 Milano, Italy

IRCCS Ospedale San Raffaele; 🇮🇹 Milano, Italy

Ospedale ASST Fatebenefratelli Sacco; 🇮🇹 Milano, Italy

ULSS 3 Veneto; 🇮🇹 Mirano, Italy

Azienda Ospedaliero-Universitaria; 🇮🇹 Modena, Italy

Azienda Ospedaliero-Universitaria Federico II; 🇮🇹 Napoli, Italy

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale; 🇮🇹 Napoli, Italy

Ospedale Maggiore della Carità; 🇮🇹 Novara, Italy

IOV Istituto Oncologico Veneto IRCCS; 🇮🇹 Padova, Italy

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Italy

IRCCS - ICS Maugeri; 🇮🇹 Pavia, Italy

Clinica Ospedaliero - Universitaria Policlinico Umberto I; 🇮🇹 Roma, Italy

Policlinico Universitario Campus Bio-Medico; 🇮🇹 Roma, Italy

Policlinico Universitario Fondazione Agostino Gemelli; 🇮🇹 Roma, Italy

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Italy