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

Conditions: 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

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.

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 criteria:
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.

Keywords: hr+/her2- advanced breast cancer hr+/her2- metastatic breast cancer palbociclib ribociclib abemaciclib cdk4/6i cyclin-dependent kinase 4/6 inhibitors metastatic breast cancer