Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial.

Background: Patients with EGFR-mutated non-small-cell lung cancer (NSCLC) and MET amplification as a mechanism of resistance to first-line osimertinib have few treatment options. Here, we report the primary analysis of the phase 2 INSIGHT 2 study evaluating tepotinib, a highly selective MET inhibitor, combined with osimertinib in this population.

Methods: This open-label, phase 2 study was conducted at 179 academic centres and community clinics in 17 countries.

A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205.

Background: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication.

Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial.

Importance: MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.

Objective: To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study.

Design, Setting, And Participants: The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021.

Excess of blood eosinophils prior to therapy correlates with worse prognosis in mesothelioma.

Background: Only a fraction of patients with malignant pleural mesothelioma (MPM) will respond to chemo- or immunotherapy. For the majority, the condition will irremediably relapse after 13 to 18 months. In this study, we hypothesized that patients' outcome could be correlated to their immune cell profile.

New Implications of Patients' Sex in Today's Lung Cancer Management.

This paper describes where and how sex matters in today's management of lung cancer. We consecutively describe the differences between males and females in lung cancer demographics; sex-based differences in the immune system (including the poorer outcomes in women who are treated with immunotherapy but no chemotherapy); the presence of oncogenic drivers and the response to targeted therapies according to sex; the greater benefit women derive from lung cancer screening and why they get screened less; and finally, the barriers to smoking cessation that women experience. We conclude that sex is an important but often overlooked factor in modern-day thoracic oncology practice.

External Validation of a Breath-Based Prediction Model for Malignant Pleural Mesothelioma.

During the past decade, volatile organic compounds (VOCs) in exhaled breath have emerged as promising biomarkers for malignant pleural mesothelioma (MPM). However, as these biomarkers lack external validation, no breath test for MPM has been implemented in clinical practice. To address this issue, we performed the first external validation of a VOC-based prediction model for MPM.

Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a fatal cancer type that affects the membranes lining the lungs, and is causally associated with asbestos exposure. Until recently, the first-line treatment consisted of a combination of chemotherapeutics that only had a limited impact on survival, and had not been improved in decades. With the recent approval of combined immune checkpoint inhibition for MPM, promising new immunotherapeutic strategies are now emerging for this disease.

INSIGHT 2: a phase II study of tepotinib plus osimertinib in -amplified NSCLC and first-line osimertinib resistance.

amplification amp), a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors, occurs in up to 30% of patients with non-small-cell lung cancer (NSCLC) progressing on first-line osimertinib. Combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor, may overcome amp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic -mutant NSCLC and acquired resistance to first-line osimertinib and amp, determined centrally by fluorescence hybridization (gene copy number ≥5 and/or ≥2) at time of progression.

Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice.

Purpose: Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups.

Patients And Methods: This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases.

Recent developments in the treatment of small cell lung cancer.

Small cell lung cancer (SCLC) comprises about 15% of all lung cancers. It is an aggressive disease, with early metastasis and a poor prognosis. Until recently, SCLC treatment remained relatively unchanged, with chemotherapy remaining the cornerstone of treatment.

DNA Methylation as a Diagnostic Biomarker for Malignant Mesothelioma: A Systematic Review and Meta-Analysis.

Malignant mesothelioma is an aggressive cancer type linked to asbestos exposure. Because of several intrinsic challenges, mesothelioma is often diagnosed in an advanced disease stage. Therefore, there is a need for diagnostic biomarkers that may contribute to early detection.

Prognostic and Predictive Biomarkers in Non-Small Cell Lung Cancer Patients on Immunotherapy-The Role of Liquid Biopsy in Unraveling the Puzzle.

In the last decade, immunotherapy has been one of the most important advances in the non-small cell lung cancer (NSCLC) treatment landscape. Nevertheless, only a subset of NSCLC patients benefits from it. Currently, the only Food and Drug Administration (FDA) approved diagnostic test for first-line immunotherapy in metastatic NSCLC patients uses tissue biopsies to determine the programmed death ligand 1 (PD-L1) status.

Caspr2 autoantibody-associated Morvan syndrome predating thymoma relapse by 30 months.

Morvan's syndrome (MoS) is a rare autoimmune disorder characterized by central nervous system involvement, autonomic dysfunction and peripheral nerve hyperexcitability. MoS is believed to be caused by autoantibodies targeting contactin-associated protein 2 (Caspr2), a subunit of the neuronal voltage-gated potassium channel (VGKC) complex, usually in association with thymoma, less commonly with other malignancies. This case highlights an exceptional case of severe sleep disturbances and behavioural changes due to MoS, in a patient who would present with and be treated successfully for a second relapse of thymoma 30 months later.

Correction: A Flare for the Unexpected: Bone Flare as Response to Tyrosine Kinase Inhibitor Treatment in a Lung Cancer Patient.

[This corrects the article DOI: 10.5334/jbsr.1907.

Tepotinib in Non-Small-Cell Lung Cancer with Exon 14 Skipping Mutations.

Background: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population.

Methods: In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed exon 14 skipping mutation.

A Flare for the Unexpected: Bone Flare as Response to Tyrosine Kinase Inhibitor Treatment in a Lung Cancer Patient: New osteoblastic bone lesions in a lung cancer patient may represent bone flare and should not be misdiagnosed as disease progression.

We report the case of a 72-year-old female never-smoker with stage IV endothelial growth factor receptor (EGFR) mutated lung adenocarcinoma. This patient was started on first line tyrosine kinase inhibitor (TKI) and seemingly developed new bone metastases under this treatment. As there was a remarkable discrepancy between the partial response seen in the primary tumor and non-osseous metastatic locations, the possibility of a bone flare phenomenon was considered.

Cancer in the time of COVID-19: expert opinion on how to adapt current practice.

https://bit.ly/2JR2IoT

Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients.

(1) Background: Therapeutic blocking of the interaction between programmed death-1 (PD-1) with its ligand PD-L1, an immune checkpoint, is a promising approach to restore the antitumor immune response. Improved clinical outcomes have been shown in different human cancers, including non-small cell lung cancer (NSCLC). Unfortunately, still a high number of NSCLC patients are treated with immunotherapy without obtaining any clinical benefit, due to the limitations of PD-L1 protein expression as the currently sole predictive biomarker for clinical use; (2) Methods: In this study, we applied mass spectrometry imaging (MSI) to discover new protein biomarkers, and to assess the possible correlation between candidate biomarkers and a positive immunotherapy response by matrix-assisted laser desorption/ionization (MALDI) MSI in 25 formalin-fixed paraffin-embedded (FFPE) pretreatment tumor biopsies (Biobank@UZA); (3) Results: Using MALDI MSI, we revealed that the addition of neutrophil defensin 1, 2 and 3 as pretreatment biomarkers may more accurately predict the outcome of immunotherapy treatment in NSCLC.

The art of obtaining a high yield of cell-free DNA from urine.

Although liquid biopsies offer many advantages over tissue biopsies, they are not yet standard practice. An important reason for the lack of implementation is the unavailability of well standardized techniques and guidelines, especially for pre-analytical conditions which are an important factor causing the current sensitivity issues. To overcome these limitations, we investigated the effect of several pre-analytical conditions on the concentration of cell-free DNA (cfDNA) and cellular genomic DNA (gDNA) contamination.

Nivolumab and anti-HCV activity, a case report.

Exhaustion of antigen-specific T-cells in order to escape immune destruction is frequently seen in chronic viral infection and different types of cancer. Blockade of overexpressed negative co-stimulatory pathways, a process known as immune checkpoint modulation, is a promising novel therapy that could improve the treatment of liver diseases with features of T cell exhaustion. We present a case of a 54-year-old hepatitis C virus (HCV) positive patient with an acute flare of hepatitis during nivolumab treatment for a stage IV lung carcinoma, an anti-programmed death-1 (PD-1) immunotherapy.

Local treatment of stage IIIA-N2 nonsmall cell lung cancer: surgery and/or radiotherapy.

Purpose Of Review: Controversy exists regarding the optimal treatment of patients with stage IIIA-N2 nonsmall cell lung cancer because of its heterogeneity. Patients are at risk for both local and distant disease relapse after primary local treatment. However, there may be a window of opportunity for surgery, if mediastinal downstaging has been obtained after induction therapy.

Mortality after lung transplantation: a single-centre cohort analysis.

Detailed data on postoperative death in lung transplant (LTx) recipients are lacking. Therefore, we investigated all deaths after LTx in a large, single-centre, 25-year follow-up cohort. Prevalence, time, place and cause of death (COD) were retrospectively analysed for all patients undergoing primary LTx between July 1991 and December 2015 in our centre.

A randomized phase II study of pleurectomy/decortication preceded or followed by (neo-)adjuvant chemotherapy in patients with early stage malignant pleural mesothelioma (EORTC 1205).

Radical multimodality treatment for malignant pleural mesothelioma (MPM) is controversial, with intense debate (but lack of data) about which surgical procedure to perform [extrapleural pneumonectomy (EPP) or pleurectomy/decortication (PD)], if any. In order to perform a randomized comparison, the most optimal sequence of surgery and chemotherapy should be determined. EORTC 1205 is a clinical trial randomizing between upfront surgery, followed by chemotherapy (cisplatin plus pemetrexed) and deferred surgery, following neoadjuvant chemotherapy in early stage (T1-3 N0-2 M0) MPM (irrespective of histological subtype).