First-line MET tyrosine kinase inhibitors versus immunotherapy ± chemotherapy for patients with MET exon 14 skipping mutant metastatic NSCLC.

Purpose: First-line treatment options for MET exon 14 skipping (METex14) mutant metastatic non-small cell lung cancer (NSCLC) vary due to differences in drug approvals and clinical experience. This study investigates factors influencing outcomes with first-line MET tyrosine kinase inhibitors (TKI) versus immune checkpoint inhibitors (ICI)±chemotherapy.

Experimental Design: Clinicopathologic data were collected from patients with metastatic METex14 mutant NSCLC receiving first-line MET TKI or ICI±chemotherapy at five centers.

Prognostic immunoinflammatory and transcriptomic profiles in patients with pleural mesothelioma undergoing immunotherapy.

Aim: A translational multiscale approach, encompassing tumor immune microenvironment (TIME), circulating immune-inflammatory benchmarks, and transcriptomic profiles, was undertaken to identify prognostic biomarkers of immunotherapy (IT) efficacy in patients with advanced pleural mesothelioma (PM).

Methods: Advanced PM patients ( = 17) treated with nivolumab plus ipilimumab were prospectively enrolled in the FIL-QI 2021 study. Baseline blood and tumor samples were analyzed for immune subsets and functional markers (Granzyme B, Ki67) by flow cytometry, cytokines by multiplex ELISA, TILs and PD-L1 by immunohistochemistry, and gene expression by nanostring.

Fusion as Resistance Mechanism to Osimertinib in -Mutated NSCLC: A Case Report and Review of Literature.

Despite the efficacy of osimertinib in the first-line treatment of advanced -mutated NSCLC, the development of resistance is nearly inevitable. mutations and fusions are reported in 1% to 3% of patients with -mutated NSCLC receiving osimertinib and represent potential targetable alterations. In this case report, we discuss the rationale for EGFR-MEK co-inhibition in a patient with -mutated NSCLC treated with osimertinib that developed a fusion at progression.

The effects of race on anti-PD-(L)1 monoclonal antibodies in non-small cell lung cancer: A systematic literature review and meta-analysis.

Introduction: Non-small cell lung cancer (NSCLC) represents approximately 85 % of lung cancers, with five-year survival only 4.5 % for metastatic disease. Programmed death (ligand)-1 (PD-[L]1) inhibitors have advanced NSCLC treatment, but patient demographics can potentially affect clinical outcomes.

Circulating tumor DNA dynamic variation predicts sotorasib efficacy in KRASp.G12C-mutated advanced non-small cell lung cancer.

Background: The objective of this study was to investigate the correlation between circulating tumor DNA (ctDNA) KRAS G12C-mutation dynamic variations and treatment outcomes in patients with advanced non-small cell lung cancer (NSCLC) receiving sotorasib therapy in a real-world setting.

Methods: Peripheral blood samples were prospectively collected from 32 patients at baseline, at cycle 3, and then at each radiologic assessment during sotorasib treatment. Both tissue and plasma samples were analyzed by using ultra-deep, customized next-generation sequencing (NGS) assays.

Molecular heterogeneity of small cell lung cancer and new therapeutic possibilities: a narrative review of the literature.

Background And Objective: Small cell lung cancer (SCLC) is an aggressive disease commonly occurring in individuals with a history of heavy smoking. Despite recent approvals of chemotherapy and immunotherapy in the first-line treatment of extensive-stage SCLC, it maintains a poor prognosis. Moreover, only a small percentage of patients benefits from the addition of immunotherapy to platinum-based chemotherapy.

A prospective study on clinicians' attitudes and survival outcomes for patients with advanced NSCLC and poor performance status in the immunotherapy era: PICASO (GOIRC-04-2020).

Background: Therapeutic strategies for patients with advanced NSCLC and an ECOG performance status (PS) 2 at diagnosis are supported by limited evidence.

Patients And Methods: We led a prospective, observational study in 20 Italian centers on patients with advanced NSCLC and ECOG PS 2. Patients with EGFR mutations, ALK fusions or receiving first-line targeted treatments were excluded.

Carboplatin, etoposide, atezolizumab, and bevacizumab in the first-line treatment of patients with extensive stage small-cell lung cancer: the GOIRC-01-2019 CeLEBrATE study.

Background: The addition of a programmed death-ligand 1 (PD-L1) inhibitor, either atezolizumab or durvalumab, to platinum-etoposide prolonged survival in a limited subset of patients with extensive-stage small-cell lung cancer (ES-SCLC). Preclinical studies demonstrated synergistic antitumor activity of combined vascular endothelial growth factor receptor and PD-L1 inhibition in SCLC. Since bevacizumab added to platinum-etoposide was safe and active in ES-SCLC, we investigated the efficacy of atezolizumab, bevacizumab, carboplatin, and etoposide as first-line treatment of ES-SCLC.

Correction: Cavazzoni et al. Pemetrexed Enhances Membrane PD-L1 Expression and Potentiates T Cell-Mediated Cytotoxicity by Anti-PD-L1 Antibody Therapy in Non-Small-Cell Lung Cancer. 2020, , 666.

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Circulating tumor DNA monitoring in advanced mutated melanoma (LIQUID-MEL).

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic melanoma, but a percentage of patients did not show benefit. Circulating tumor DNA (ctDNA) has emerged as a potential non-invasive tool for monitoring disease evolution and treatment response. The present study aimed to evaluate the clinical utility of ctDNA dynamics in patients with metastatic melanoma receiving ICIs, while exploring its role in the oncological course.

Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer.

Osimertinib-a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor-is recommended as adjuvant therapy for resected stage IB-IIIA epidermal growth factor receptor-mutated non-small-cell lung cancer, based on significant disease-free survival (DFS) and overall survival improvement shown in the previously reported phase 3 ADAURA trial. A trend toward an increased DFS event rate after completion of 3 years adjuvant treatment in ADAURA suggests that some patients may benefit from longer adjuvant osimertinib treatment. We therefore explored whether tumor-informed, circulating tumor DNA-based, molecular residual disease (MRD) could predict recurrence in an exploratory post hoc analysis of 220 patients (n = 112 osimertinib; n = 108 placebo) from ADAURA.

NGS detection of gene rearrangements and METexon14 mutations in liquid biopsy of advanced NSCLC patients: A study of two Italian centers.

Introduction: ctDNA is a useful tool for NGS molecular profiling in advanced NSCLC patients. Its clinical applicability in patients with gene rearrangements is still limited due to a lower detection rate of these types of alterations compared to single SNVs or small indels. To this purpose, we performed a study in two Italian centers to assess the concordance between tissue and plasma samples in the detection of genes fusions (, , ) and mutations in advanced NSCLC patients.

Impact of edoxaban-related adverse events in patients with cancer experiencing venous thromboembolism during antineoplastic therapy: Results of the phase IV EDOI study (GOIRC-05-2018).

Background: The oral factor Xa inhibitor, edoxaban, is effective and safe in cancer-associated Venous Thromboembolism (VTE) treatment. The EDOI study aims to evaluate compliance and quality of life (QoL) in patients with cancer-associated VTE treated with edoxaban during antineoplastic care.

Material And Methods: The EDOI was a multicentre phase IV, single-arm study.

Unraveling the link between cholesterol and immune system in cancer: From biological mechanistic insights to clinical evidence. A narrative review.

Cholesterol and its metabolism seem to be involved not only in cancer progression but also in immune cells activity. In this comprehensive review, we summarize preclinical, translational, and clinical evidence regarding the crucial role of cholesterol and its metabolism in regulating the immune response against cancer cells, shedding light on the multifaceted mechanisms by which cholesterol influences immune cell function and anti-tumor immunity. By synthesizing findings from preclinical studies, we have elucidated the impact of cholesterol on immune cell activation, differentiation, and effector functions.

An open-label, randomized phase III study of early switch maintenance vs delayed second-line nivolumab in advanced stage squamous non-small cell lung cancer (NSCLC) patients after standard first-line platinum-based chemotherapy-EDEN trial GOIRC 04-2016.

Background: As for squamous (Sq)-NSCLC, Checkmate-017 trial showed a significant overall survival (OS) improvement in favor of Nivolumab (Nivo) over Docetaxel in 2nd-line. We hypothesized that anticipating Nivo use, as early switch maintenance after 1st-line chemotherapy (CHT), might have improved survival as compared to delayed 2nd-line treatment.

Methods: EDEN was an open-label, 2-arm, phase III study which randomized (1:1) stage IIIB/IV Sq-NSCLC pts non-progressive after 1st-line platinum-based CHT, to receive early Nivo as switch maintenance (Arm A) or standard best supportive care followed by 2nd-line Nivo at disease progression (Arm B).

Longitudinal Blood Immune-Inflammatory and Radiomic Profiling to Decode Different Patterns of Acquired Resistance to Immunotherapy in Patients with NSCLC.

Purpose: To uncover the underpinnings of acquired resistance (AR) to immunotherapy (IO), we determined whether distinctive clinicopathologic, radiomic, and peripheral blood (PB) immune-inflammatory features reflect oligo- and systemic (sys)-AR in patients with advanced non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor therapy.

Experimental Design: On 105 consecutive patients with IO-treated advanced NSCLC, PB immunophenotypes, cytokines, and CT-derived radiomic features (RF), extracted from primary and merged metastatic lesions, were prospectively collected at baseline (T0) and at the first disease assessment (T1, 9-12 weeks), and their Δ variation [(T1-T0)/T0] was computed. AR, defined as progression after the initial response (complete/partial) or stable disease ≥6 months, was subdivided according to the number of new and/or progressive lesions in oligoAR (≤3) and sysAR (>3).

Body composition derangements in lung cancer patients treated with first-line pembrolizumab: A multicentre observational study.

Background: While immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non-small-cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long-lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre-treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first-line pembrolizumab monotherapy for advanced NSCLC.

Development and validation of a new tool to estimate early mortality in patients with advanced cancer treated with immunotherapy.

Background: Immune checkpoint inhibitors (ICIs) are standard treatments for advanced solid cancers. Resistance to ICIs, both primary and secondary, poses challenges, with early mortality (EM) within 30-90 days indicating a lack of benefit. Prognostic factors for EM, including the lung immune prognostic index (LIPI), remain underexplored.

Liquid Biopsy and 18F-FDG PET/CT Derived Parameters as Predictive Factors of Osimertinib Treatment in Advanced EGFR-Mutated NSCLC.

Objectives: Despite the outstanding results achieved by osimertinib for the treatment of advanced EGFR-mutated NSCLC, the development of resistance is almost inevitable. While molecular mechanism responsible for osimertinib resistance are being mostly revealed, the definition of predictive biomarkers is crucial in order to identify patients at higher risk of progression and optimize treatment strategy.

Materials And Methods: This is a prospective single-center study aimed to assess the potential role of liquid biopsy and 18F-FDG PET/CT derived metabolic parameters as noninvasive predictive biomarkers of osimertinib outcomes in advanced EGFR-mutated NSCLC patients.

MET alterations as resistance mechanisms of dabrafenib-trametinib in BRAF p.V600E mutated non-small cell lung cancer patient.

The combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and MEK inhibition in NSCLC are still unknown. Herein, we report a case of a 76-year-old man with a history of smoking who was diagnosed with BRAF V600E-mutant lung adenocarcinoma (PD-L1 > 50%) and subsequently candidate to first-line therapy with pembrolizumab.

Differential impact of lipid profile according to neutrophil-to-lymphocyte ratio status in patients with advanced cancer treated with immunotherapy.

To investigate the different impact of each component of lipid profile in advanced cancer patients treated with immune checkpoints inhibitors (ICIs) according to neutrophil-to-lymphocyte ratio (NLR) value. We retrospectively collected total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDL), high-density lipoproteins (HDL). 407 patients were enrolled.