Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: the IMMINENT study.

Introduction: To date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test for driver alterations to identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, with the aim of assessing the distribution and the real-world frequency of gene alterations and their correlation with patient characteristics, we present the outcomes obtained using FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) NGS-based profiling in a nationwide initiative for advanced NSCLC patients.

Radical resection in a patient with stage IIIA non-small cell lung cancer with the exon 19 deletion mutation after neoadjuvant targeted therapy with osimertinib: a case report.

Background: With the advent of targeted therapies, the survival rates of patients with locally advanced lung cancer have significantly improved. However, there is limited research on the efficacy of neoadjuvant targeted therapy in resectable advanced non-small cell lung cancer (NSCLC) patients with positive driver genes. This article reports a case of stage IIIA NSCLC with an epidermal growth factor receptor () 19del mutation that successfully underwent radical lung cancer surgery following neoadjuvant targeted therapy.

Efficacy of osimertinib and the role of sequential liquid biopsy in patients diagnosed with NSCLC harboring EGFR and BRAF mutations at baseline: insights from two case reports.

Epidermal Growth Factor Receptor (EGFR) and B-Raf (BRAF) mutations are two of the most important drivers identified in non-small-cell lung cancer (NSCLC). This report highlights two cases of patients diagnosed with metastatic NSCLC bearing concurrent EGFR and BRAF mutations at baseline and treated with osimertinib as first-line treatment. Molecular profiling was conducted in the tissue and plasma at the time of initial diagnosis, and subsequent repeated liquid biopsy examinations were planned after 10 days, 28 days, and at the time of radiological progression in the frame of the prospective translational study REM.

Aumolertinib in NSCLC with leptomeningeal involvement, harbouring concurrent exon 19 deletion and comutation: a case report.

Background: Aumolertinib (HS-10296), a 3rd-generation epidermal growth factor receptor () tyrosine kinase inhibitor (TKI), has been shown to have efficacy in treating tumors harboring sensitive mutations: in-frame deletions or insertions within exon 19 deletion (19Del) and the exon 21 L858R mutation and T790M resistance mutation. Research has shown that tumor protein p53 () mutations and leptomeningeal metastases (LM) are associated with reduced responsiveness and a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC) who have received targeted therapy with EGFR-TKIs. The mutation is a common concomitant mutation of amplification in solid tumors.

Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational study.

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration.

Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020.

SCLC Treatment in the Immuno-Oncology Era: Current Evidence and Unmet Needs.

Small cell lung cancer (SCLC) represents about 13%-15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the combination of immunotherapy (atezolizumab, durvalumab with or without tremelimumab, and pembrolizumab) with double platinum chemotherapy, with practice-changing results.

Multicenter Real-World Study on Effectiveness and Early Discontinuation Predictors in Patients With Non-small Cell Lung Cancer Receiving Nivolumab.

Background: Real-world (RW) evidence on nivolumab in pretreated patients with non-small cell lung cancer (NSCLC) by matching data from administrative health flows (AHFs) and clinical records (CRs) may close the gap between pivotal trials and clinical practice.

Methods: This multicenter RW study aims at investigating median time to treatment discontinuation (mTTD), overall survival (mOS) of nivolumab in pretreated patients with NSCLC both from AHF and CR; clinical-pathological features predictive of early treatment discontinuation (etd), budget impact (BI), and cost-effectiveness analysis were investigated; mOS in patients receiving nivolumab and docetaxel was assessed.

Results: Overall, 237 patients with NSCLC treated with nivolumab were identified from AHFs; mTTD and mOS were 4.

Liquid biopsy and non-small cell lung cancer: are we looking at the tip of the iceberg?

The possibility to analyse the tumour genetic material shed in the blood is undoubtedly one of the main achievements of translational research in the latest years. In the modern clinical management of advanced non-small cell lung cancer, molecular characterisation plays an essential role. In parallel, immunotherapy is widely employed, but reliable predictive markers are not available yet.

Clinical outcomes of NSCLC patients experiencing early immune-related adverse events to PD-1/PD-L1 checkpoint inhibitors leading to treatment discontinuation.

Background: The prognostic relevance of early immune-related adverse events (irAEs) in patients affected by non-small cell lung cancer (NSCLC) upon immunotherapy is not fully understood.

Methods: The Leading to Treatment Discontinuation cohort included 24 patients experiencing severe irAEs after one of two administrations of single anti-PD-1/PD-L1 in any line setting for metastatic NSCLC between November 2015 and June 2019. The control cohort was composed of 526 patients treated with single anti-PD-1/PD-L1 in any line setting with no severe irAE reported.

Comparing immunotherapies to other frequently used treatments of gastric cancer.

: Although standard doublet chemotherapy represents the upfront gold standard to increase survival and improve quality of life of gastric cancer patients, overall improvements in long-term outcomes are modest and novel treatments are urgently needed. Among these, immunotherapy is an increasingly attractive option.: A number of clinical trials have shown that checkpoint inhibitors may be of value, but many unclear issues remain controversial and should be promptly untangled.

Synaptophysin expression in mutated advanced colorectal cancers identifies a new subgroup of tumours with worse prognosis.

Background: Neuroendocrine differentiation has been extensively associated with worse prognosis and to mechanisms of therapy resistance in several epithelial cancers. A high prevalence of neuroendocrine differentiation was recently described in mutated (BRAFmt) metastatic colorectal cancers (mCRCs) but no data are available about its prognostic impact in this setting.

Methods: We assessed synaptophysin immunohistochemical expression in a multi-institutional series of 159 BRAFmt mCRCs with matched clinical and pathological information.

Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome.

Background: Characterization of tumor-related genetic alterations is promising for the screening of new predictive markers in non-small cell lung cancer (NSCLC). Aim of the study was to evaluate prognostic and predictive role of most frequent tumor-associated genetic alterations detected in plasma before starting immune checkpoint inhibitors (ICIs).

Methods: Between January 2017 and October 2019, advanced NSCLC patients were prospectively screened with plasma next-generation sequencing (NGS) while included in two trials: VISION (NCT02864992), using Guardant360 test, and MAGIC (Monitoring Advanced NSCLC through plasma Genotyping during Immunotherapy: Clinical feasibility and application), using Myriapod NGS-IL 56G Assay.

Case Report: A Metabolic Complete Response to Upfront Osimertinib in a Smoker Non-Small Cell Lung Cancer Patient Harbouring G719A/V769M Complex Mutation.

Complex mutations are rare in non-small cell lung cancer (NSCLC). Limited clinical evidence is available on the efficacy of tyrosine kinase inhibitors (TKIs) in patients with NSCLC harbouring these uncommon mutations. Here, we reported the case of a complete metabolic response in a patient with advanced NSCLC carrying the uncommon G719A/V769M complex mutation treated with the first-line osimertinib.

Clinical Impact of Plasma and Tissue Next-Generation Sequencing in Advanced Non-Small Cell Lung Cancer: A Real-World Experience.

Background: Targeted agents have improved the outcome of a subset of non-small cell lung cancer (NSCLC). Molecular profiling by next-generation sequencing (NGS) allows screening for multiple genetic alterations both in tissue and in plasma, but limited data are available concerning its feasibility and impact in real-world clinical practice.

Methods: Patients with advanced NSCLC consecutively referring to our Institution for potential eligibility to VISION trial (NCT02864992) were prospectively enrolled.

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study.

Introduction: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab.

CK7 and consensus molecular subtypes as major prognosticators in BRAF mutated metastatic colorectal cancer.

Background: BRAF mutated metastatic colorectal cancer (mCRC) is a subtype (10%) with overall poor prognosis, but the clinical experience suggests a great heterogeneity in survival. It is still unexplored the real distribution of traditional and innovative biomarkers among BRAF mutated mCRC and which is their role in the improvement of clinical prediction of survival outcomes.

Methods: Data and tissue specimens from 155 BRAF mutated mCRC patients treated at eight Italian Units of Oncology were collected.

A validated prognostic classifier for BRAF-mutated metastatic colorectal cancer: the 'BRAF BeCool' study.

Background: Despite the well-known negative prognostic value of the BRAF mutation in patients with metastatic colorectal cancer (mCRC), its outcome is quite heterogeneous, and the basis for this prognostic heterogeneity should be better defined.

Methods: Two large retrospective series of BRAF-mutated mCRC from 22 institutions served as an exploratory and validation set to develop a prognostic score. The model was internally and externally validated.

Peripheral Blood Markers Identify Risk of Immune-Related Toxicity in Advanced Non-Small Cell Lung Cancer Treated with Immune-Checkpoint Inhibitors.

Background: Immune-checkpoint inhibitors (ICIs) are now standard of care for advanced non-small cell lung cancer (NSCLC). Unfortunately, many patients experience immune-related adverse events (irAEs), which are usually mild and reversible, but they require timely management and may be life threatening. No predictive markers of irAEs are available.

From Diagnostic-Therapeutic Pathways to Real-World Data: A Multicenter Prospective Study on Upfront Treatment for -Positive Non-Small Cell Lung Cancer (MOST Study).

Introduction: Gefitinib, erlotinib, and afatinib represent the approved first-line options for epidermal growth factor receptor ()-mutant non-small cell lung cancer (NSCLC). Because pivotal trials frequently lack external validity, real-world data may help to depict the diagnostic-therapeutic pathway and treatment outcome in clinical practice.

Methods: MOST is a multicenter observational study promoted by the Veneto Oncology Network, aiming at monitoring the diagnostic-therapeutic pathway of patients with nonsquamous -mutant NSCLC.