The Impact of Concordance Between Liquid and Tissue Biopsy for Actionable Mutations: Insights from the Rome Trial.

Purpose: This analysis evaluated the influence of tissue and liquid biopsy concordance on outcomes in patients enrolled in the ROME Trial.

Experimental Design: The ROME trial, a phase II multicenter study, enrolled 1,794 patients with advanced solid tumors. Next-generation sequencing (NGS) was performed on tissue and liquid biopsies using FoundationOne CDx and FoundationOne Liquid CDx, A centralized Molecular Tumor Board (MTB) reviewed results to identify actionable alterations, with 400 patients randomized to tailored therapy (TT) or standard-of-care (SoC).

Impact of Drug-Drug Interactions on Clinical Outcomes in Metastatic Melanoma Patients Treated With Combined BRAF/MEK Inhibitors: A Real-World Study.

The unique pharmacokinetics of BRAF and MEK inhibitors make patients vulnerable to drug-drug interactions (DDIs), which may compromise treatment efficacy in metastatic melanoma. This study evaluates the impact of DDIs on clinical outcomes in patients with metastatic melanoma treated with BRAF/MEK inhibitors. This multicenter, observational, retrospective study assessed DDIs using the Drug-PIN software.

Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors.

A comparative analysis of Denosumab (DMAB) and Zoledronic Acid (ZA) was conducted in a real-world cohort of 864 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer with bone metastases, who were undergoing CDK4/6 inhibitors plus endocrine therapy. We evaluated the time to first skeletal-related events (SREs), progression-free survival (PFS), and overall survival (OS). To adjust for confounding variables, we utilized propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methodologies.

ESR1 testing on FFPE samples from metastatic lesions in HR + /HER2- breast cancer after progression on CDK4/6 inhibitor therapy.

Mutations in ESR1 play a critical role in resistance to endocrine therapy (ET) in hormone receptor-positive (HR +)/HER2- metastatic breast cancer (MBC). Testing for ESR1 mutations is essential for guiding treatment with novel oral selective estrogen receptor degraders (SERDs) like elacestrant or camizestrant. While most studies have utilized liquid biopsy (LB) for mutation detection, the role of formalin-fixed paraffin-embedded (FFPE) tissue biopsy in this context remains unclear.

Prognostic impact of tumor-infiltrating lymphocytes in HER2+ metastatic breast cancer receiving first-line treatment.

Breast cancer (BC) is a leading cause of death among women, with approximately 30% HER2-positive (HER2+). Although HER2-targeted therapies have improved outcomes for patients with HER2+ metastatic breast cancer (mBC), clinical challenges and prognostic variability remain. Tumor-infiltrating lymphocytes (TILs) have emerged as prognostic and predictive biomarkers in various tumors, including BC, but their role in HER2+ mBC is poorly understood.

Association between body composition parameters and treatment-related toxicities in patients with metastatic breast cancer receiving cyclin-dependent kinase 4 and 6 inhibitors.

Background & Aims: Nowadays, limited data or no data are available on body composition changes and the development of treatment-related toxicities in metastatic breast cancer (MBC) patients treated with innovative and promising anticancer therapies, including cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Therefore, we evaluated in MBC treated with CDK4/6 inhibitors changes in adiposity and muscularity before and after treatment and whether the changes in these parameters were associated with toxicities, dose reduction or treatment discontinuation.

Methods: We considered ER+/HER2- MBC patients undergoing treatment with CDK 4/6 inhibitors, collected clinical data and registered the number and type of toxicities, dose reduction due to adverse events and the rate of discontinuation.

Survival Following CDK4/6 Inhibitor Therapy for Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer.

Importance: Endocrine therapy (ET) combined with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) agents is the standard first-line treatment for patients with hormone receptor-positive, ERBB2 (formerly HER2 or HER2/neu)-negative metastatic breast cancer. However, optimal therapy after tumor progression to ET plus CDK4/6i remains unclear.

Objective: To evaluate progression-free survival (PFS) and overall survival (OS) in the clinical practice setting in patients with hormone receptor-positive, ERBB2-negative metastatic breast cancer following progression with ET plus CDK4/6i.

Real life outcome analysis of breast cancer brain metastases treated with Trastuzumab Deruxtecan.

Tumor dissemination to the central nervous system (CNS) is almost a rule in the treatment journey of advanced HER2+ breast cancer (BC). Recent results demonstrated high intracranial efficacy with Trastuzumab Deruxtecan (T-DXd). However, a real-world evidence is lacking in literature.

Clinical impact of drug-drug interactions on abemaciclib in the real-world experience of AB-ITALY study.

Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2- advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs' impact, and toxicities of abemaciclib combined with endocrine therapy in a real-world setting.

Clinical implications of the Drug-Drug Interaction in Cancer Patients treated with innovative oncological treatments.

In the last two-decades, innovative drugs have revolutionized cancer treatments, demonstrating a significant improvement in overall survival. These drugs may present several pharmacokinetics interactions with non-oncological drugs, and vice versa, and, non-oncological drugs can modify oncological treatment outcome both with pharmacokinetic interaction and with an "off-target impact" on the tumor microenvironment or on the peripheral immune response. It's supposed that the presence of a drug-drug interaction (DDI) is associated with an increased risk of reduced anti-tumor effects or severe toxicities.

Assessing risks and knowledge gaps on the impact of systemic therapies in early breast cancer on female fertility: A systematic review of the literature.

The therapeutic landscape for early breast cancer (eBC) has expanded by introducing novel anticancer agents into clinical practice. During their reproductive years, women with eBC should be informed of the potential risk of premature ovarian insufficiency (POI) and infertility with the proposed systemic therapy. Although the topic of female fertility is becoming increasingly relevant in patients with cancer, limited information is available on the gonadotoxicity of new agents available for eBC treatment.

Immune responses and clinical outcomes following the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in advanced breast cancer patients receiving targeted therapies: a prospective study.

Purpose: Metastatic breast cancer patients are the most prevalent oncology population with advanced disease facing COVID-19 pandemic. Immune responses after mRNA-based vaccination during treatment with CDK4/6 inhibitors or HER2-directed agents remain unclear. We conducted a prospective analysis to elucidate changes in antibody titers and lymphocyte counts following full course of mRNA-BNT162b2 (tozinameran) vaccination in recipients undergoing these targeted therapies.

The Impact of Drug-Drug Interactions on the Toxicity Profile of Combined Treatment with BRAF and MEK Inhibitors in Patients with BRAF-Mutated Metastatic Melanoma.

Background: BRAF and MEK inhibition is a successful strategy in managing BRAF-mutant melanoma, even if the treatment-related toxicity is substantial. We analyzed the role of drug-drug interactions (DDI) on the toxicity profile of anti-BRAF/anti-MEK therapy.

Methods: In this multicenter, observational, and retrospective study, DDIs were assessed using Drug-PIN software (V 2/23).

Pathologic response and survival after neoadjuvant chemotherapy with or without pertuzumab in patients with HER2-positive breast cancer: the Neopearl nationwide collaborative study.

Purpose: Clinical trials have shown a significant increase in pathologic complete response (pCR) with the addition of pertuzumab to neoadjuvant chemotherapy for patients with early-stage HER-2 positive breast cancer. To date, limited studies have examined comparative outcomes of neoadjuvant pertuzumab in real-world setting. The Neopearl study aimed to assess comparative real-life efficacy and safety of neoadjuvant pertuzumab for these patients.

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from , a multicentric, observational study.

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available.

Circulating CD137 T Cell Levels Are Correlated with Response to Pembrolizumab Treatment in Advanced Head and Neck Cancer Patients.

Pembrolizumab, an anti-PD-1 antibody, has been approved as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma ((R/M) HNSCC). However, only a minority of patients benefit from immunotherapy, which highlights the need to identify novel biomarkers to optimize treatment strategies. CD137 T cells have been identified as tumour-specific T cells correlated with immunotherapy responses in several solid tumours.

Safety of extended interval dosing immune checkpoint inhibitors: a multicenter cohort study.

Background: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown.

Methods: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED).

Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach.

Background: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development.

The role of immune profile in predicting outcomes in cancer patients treated with immunotherapy.

Background: Despite the efficacy of immunotherapy, only a small percentage of patients achieves a long-term benefit in terms of overall survival. The aim of this study was to define an immune profile predicting the response to immune checkpoint inhibitors (ICIs).

Methods: Patients with advanced solid tumors, who underwent ICI treatment were enrolled in this prospective study.

Immune effects of CDK4/6 inhibitors in patients with HR/HER2 metastatic breast cancer: Relief from immunosuppression is associated with clinical response.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are innovative small target molecules that, in combination with endocrine therapy, have recently been employed in the treatment of patients with HR/HER2 metastatic breast cancer (mBC). In this prospective study, we investigate the impact of CDK4/6i on the immune profile of patients with HR/HER2 mBC.

Methods: Immune cell subsets were analysed using flow cytometry of peripheral blood mononuclear cells (PBMCs) isolated from patients with HR/HER2 mBC, both before and during treatment.

The Role of the CDK4/6 Inhibitor Ribociclib in Locally Advanced and Oligometastatic Hormone Receptor Positive, Her2 Negative, Advanced Breast Cancer: Case Series and Review of the Literature.

The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors to endocrine therapy has remarkably improved the outcome of patients affected with hormone receptor positive (HR+), human epidermal grow factor receptor 2 negative (HER2 -) advanced breast cancer (ABC). Ribociclib showed to be effective across most subgroups, regardless of the number and the site of metastasis. Up to 10% of patients with ABC, reported an oligometastatic condition, recently defined as a slow-volume metastatic disease with limited number and size of metastatic lesions (up to 5 and not necessarily in the same organ), potentially amenable for local treatment, aimed at achieving a complete remission status.

PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting.

Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients.

Methods: The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020.