Prognosis and biological characteristics of ER-low metastatic breast cancer: results from a multicenter cohort and the TONIC trial.

Purpose: To assess prognosis of ER-low expression and its dynamics in HER2- metastatic breast cancer (BC) and to compare sensitivity to nivolumab between ER-low and triple-negative (TN) BC.

Experimental Design: Two cohorts were analyzed: a multicenter cohort of 982 patients with HER2- metastatic BC, and one prospective cohort of 110 patients with ER<10%/HER2- metastatic BC enrolled in the TONIC trial (testing nivolumab). Endpoints were: overall survival (OS) and post-relapse survival (PRS) in the retrospective cohort; progression-free survival (PFS), OS, and clinical benefit rate (CBR) in the TONIC trial.

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).

The evolving landscape of hormone receptor-positive/HER2-negative metastatic breast cancer (EVOLVE): An Italian Delphi consensus report.

Background: The expanding treatment landscape for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) has led to the emergence of new "grey areas" not covered by international guidelines, where treatment decision making is particularly challenging.

Methods: Sixteen relevant statements regarding the management of HR+ /HER2- mBC were formulated by an Executive Board and validated by a Scientific Board, composed by internationally recognized experts in the field of BC. Subsequently, 50 Italian oncologists were surveyed between May 2024 and June 2024 through the modified Delphi method, in order to capture their rate of agreement and disagreement on the proposed statements.

Immunotherapy in recurrent/metastatic head and neck squamous cell carcinoma: PD-L1 and beyond.

Head and neck squamous cell carcinoma (HNSCC) is a prominent global health concern because of its high incidence, aggressive clinical behavior, and scarce therapeutic options. The management of these neoplasms in the recurrent/metastatic setting has been revolutionized following the results of key clinical trials, leading to the advent of immunotherapeutic agents targeting the PD-1/PD-L1 axis. Despite the exciting results obtained with the new drugs, immunotherapy is helpful only in a sizable minority of patients, and there is a pressing need to identify reliable predictive biomarkers for patient selection.

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.

Key decision factors in second-line therapy: Expert insights on HR+/HER2-metastatic breast cancer post-CDK4/6 inhibitor progression.

The progression of HR+/HER2- metastatic breast cancer after treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) poses significant therapeutic challenges. Endocrine therapy (ET) remains a cornerstone of subsequent treatment, but its effectiveness depends on a nuanced understanding of clinical and genomic factors that drive therapy selection. For example, the duration of response to prior CDK4/6i therapy strongly predicts sensitivity to subsequent ET.

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.

Process management method in head and neck cancer patient care.

Management of patients with head and neck cancer (HNC) is a complex process that involves extensive knowledge on (at least) the discipline of surgery, radiation oncology, medical oncology and molecular biology. It includes prevention, cancer treatment, follow up schedule and potential risk from treatment (radiation exposure). A major point is that perhaps now more than ever process management needs to be at the center of the HNC care.

Cost-effectiveness of cetuximab-containing regimens for squamous cell carcinoma of the head and neck in Italy.

Aims: To investigate the differences in clinical outcomes and costs for the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) with a combined positive score (CPS) of 1-19, with pembrolizumab ± chemotherapy or a cetuximab-containing regimen (CCR) in Italy.

Methods: A naïve indirect treatment comparison was conducted, and outcomes were incorporated into a newly developed cost-utility model. Inputs were derived from clinical trials, technology appraisal reports, and published literature.

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.

Improving the multidisciplinary therapeutic management of head and neck squamous cell carcinoma: Consensus statements from an Italian expert panel.

Objective: The management of recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) poses significant clinical challenges. This study aimed to develop expert consensus statements to improve the multidisciplinary management of RM HNSCC.

Methods: A multidisciplinary team of 39 Italian experts, including medical oncologists, surgeons, radiation oncologists, radiologists, and pathologists, employed the Delphi method to achieve consensus on critical aspects of RM HNSCC management.

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.

Tolerability and Preliminary Outcomes of Adjuvant T-DM1 in HER2-Positive Breast Cancer After Neoadjuvant Therapy: The ATD Study.

Background/objectives: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting.

Exploring Genomic Biomarkers for Pembrolizumab Response: A Real-World Approach and Patient Similarity Network Analysis Reveal DNA Response and Repair Gene Mutations as a Signature.

: Single-agent immune checkpoint inhibitor (IO) therapy is the standard for non-oncogene-addicted advanced non-small cell lung cancer (aNSCLC) with PD-L1 tumor proportion score ≥ 50%. Smoking-induced harm generates high tumor mutation burden (H-TMB) in smoking patients (S-pts), while never-smoking patients (NS-pts) typically have low TMB (L-TMB) and are unresponsive to IO. However, the molecular characterization of NS-pts with H-TMB remains unclear.

Neuroendocrine neoplasms of the breast: a multicenter retrospective Italian study.

Background: The aim of our retrospective study was to describe the immunophenotypic characteristics of neuroendocrine breast neoplasm (BNEN), a peculiar and rare type of breast carcinoma.

Methods: Pathological data from 51 patients affected by BNEN were retrospectively evaluated, and 44 patients were considered eligible (7 patients with incomplete data were excluded). The patients were followed in six different Italian hospitals between 2009 and 2019.

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.

The multidisciplinary management of locally advanced rectal cancer.

Introduction: The classic paradigm for the management of locally advanced rectal cancer (LARC) consists of (chemo)radiotherapy (C)RT), total mesorectal excision, and adjuvant chemotherapy (CHT). At present, due to the high rate of distant metastasis (up to 30%), the total neoadjuvant therapy (TNT) with the administration of systemic CHT in the neoadjuvant setting has gained acceptance as standard of care.Our aim is to critically review the current literature on LARC management and summarize the different approaches recently proposed to improve clinical outcomes.