Concomitant Usage of H1-Antihistamines and Immune Checkpoint Inhibitors on Cancer Patient Survival.

Purpose: Recent research (Li et al. 2021) suggests an upregulated expression and activation of H1 receptors on macrophages in the tumor microenvironment, and concomitant H1-antihistamine use is associated with improved overall survival in patients with lung and skin cancers receiving immunotherapy. Therefore, we retrospectively evaluated the impacts of H1-antihistamine use in cancer patients during immunotherapy.

Calls to action on lung cancer management and research.

Lung cancer, the leading cause of cancer-related deaths globally, remains a pressing health issue despite significant medical advances. The New York Lung Cancer Foundation brought together experts from academia, the pharmaceutical and biotech industries as well as organizational leaders and patient advocates, to thoroughly examine the current state of lung cancer diagnosis, treatment, and research. The goal was to identify areas where our understanding is incomplete and to develop collaborative public health and scientific strategies to generate better patient outcomes, as highlighted in our "Calls to Action.

SMARCA4 deficiency and mutations are frequent in large cell lung carcinoma and are prognostically significant.

SMARCA4 mutation has emerged as a marker of poor prognosis in lung cancer and has potential predictive value in cancer treatment, but recommendations for which patients require its investigation are lacking. We comprehensively studied SMARCA4 alterations and the clinicopathological significance in a large cohort of immunohistochemically-subtyped non-small cell lung cancer (NSCLC). A total of 1416 patients was studied for the presence of SMARCA4 deficiency by immunohistochemistry (IHC).

Baveno VII criteria identify varices needing treatment in patients with hepatocellular carcinoma of different Barcelona Clinic Liver Cancer stages.

Background: Baveno VII criteria for predicting varices needing treatment (VNT) have not been tested in hepatocellular carcinoma (HCC) population. We evaluated Baveno VII consensus for VNT in HCC patients of different stages according to Barcelona Clinic Liver Cancer (BCLC) stages undergoing curative hepatectomy.

Methods: This was a prospective cohort study of patients with HCC.

Baveno VII Criteria Is an Accurate Risk Stratification Tool to Predict High-Risk Varices Requiring Intervention and Hepatic Events in Patients with Advanced Hepatocellular Carcinoma.

The Baveno VII criteria are used in patients with liver cirrhosis to predict high-risk varices in patients with liver cirrhosis. Yet its use in patients with advanced hepatocellular carcinoma (HCC) has not been validated. HCC alone is accompanied with a higher variceal bleeding risk due to its association with liver cirrhosis and portal vein thrombosis.

Overcoming immunosuppression and pro-tumor inflammation in lung cancer with combined IL-1β and PD-1 inhibition.

Inflammation in the tumor microenvironment is a complicit and known carcinogenesis driver. Inhibition of IL-1β, one of the most abundant and influential cytokines in the tumor microenvironment, may enhance the efficacy of PD-1. In a analysis of phase III cardiovascular CANTOS trial, canakinumab, a monoclonal anti-IL-1β antibody, significantly reduced lung cancer incidence.

Artificial intelligence-powered programmed death ligand 1 analyser reduces interobserver variation in tumour proportion score for non-small cell lung cancer with better prediction of immunotherapy response.

Background: Manual evaluation of programmed death ligand 1 (PD-L1) tumour proportion score (TPS) by pathologists is associated with interobserver bias.

Objective: This study explored the role of artificial intelligence (AI)-powered TPS analyser in minimisation of interobserver variation and enhancement of therapeutic response prediction.

Methods: A prototype model of an AI-powered TPS analyser was developed with a total of 802 non-small cell lung cancer (NSCLC) whole-slide images.

Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as Complementary Biomarker for Immune Checkpoint Inhibition in Non-Small-Cell Lung Cancer.

Purpose: Biomarkers on the basis of tumor-infiltrating lymphocytes (TIL) are potentially valuable in predicting the effectiveness of immune checkpoint inhibitors (ICI). However, clinical application remains challenging because of methodologic limitations and laborious process involved in spatial analysis of TIL distribution in whole-slide images (WSI).

Methods: We have developed an artificial intelligence (AI)-powered WSI analyzer of TIL in the tumor microenvironment that can define three immune phenotypes (IPs): inflamed, immune-excluded, and immune-desert.

Erratum: Epigenomic characterization of a p53-regulated 3p22.2 tumor suppressor that inhibits STAT3 phosphorylation via protein docking and is frequently methylated in esophageal and other carcinomas: Erratum.

[This corrects the article DOI: 10.7150/thno.20893.

Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050).

Objectives: To compare efficacy and safety of dacomitinib versus gefitinib as first-line therapy for EGFR mutation-positive advanced NSCLC in Asian patients enrolled in the ongoing ARCHER 1050 trial.

Materials And Methods: In this ongoing, randomized, open-label, phase 3 trial (NCT01774721), eligible patients with newly diagnosed advanced EGFR mutation-positive NSCLC were randomized (1:1) to receive oral dacomitinib 45 mg/day or oral gefitinib 250 mg/day. Randomization, by a central computer system, was stratified by race and EGFR mutation type (exon 19 deletion mutation/exon 21 L858R substitution mutation).

Canakinumab with and without pembrolizumab in patients with resectable non-small-cell lung cancer: CANOPY-N study design.

Canakinumab is a human IgGκ monoclonal antibody, with high affinity and specificity for IL-1β. The Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS) trial, evaluating canakinumab for cardiovascular disease, provided the first signal of the potential of IL-1β inhibition on lung cancer incidence reduction. Here, we describe the rationale and design for CANOPY-N, a randomized Phase II trial evaluating IL-1β inhibition with or without immune checkpoint inhibition as neoadjuvant treatment in patients with non-small-cell lung cancer.

Hepatitis Flare During Immunotherapy in Patients With Current or Past Hepatitis B Virus Infection.

Introduction: Immunotherapy has dramatically improved the survival of patients with advanced or metastatic malignancies. Recent studies suggest that immunotherapy may increase the risk of hepatitis, whereas it may also induce functional cure of chronic hepatitis B virus (HBV) infection. We evaluated the incidence of hepatitis flare, HBV reactivation, hepatitis B surface antigen (HBsAg) seroclearance or seroreversion in patients with current or past HBV infection who had received immunotherapy.

Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations.

Background: ARCHER 1050, an ongoing, randomized, open-label, phase III trial of dacomitinib versus gefitinib in newly diagnosed patients with advanced non-small-cell lung cancer (NSCLC) and an EGFR-activating mutation, reported significant improvement in overall survival (OS) with dacomitinib.

Objective: This paper reports an updated OS analysis of ARCHER 1050 after an extended follow-up.

Patients And Methods: In this multinational, multicenter trial, adults (aged ≥ 18 years or ≥ 20 years in Japan and Korea) with newly diagnosed NSCLC and EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and no history of central nervous system metastases, were randomized 1:1 to receive dacomitinib 45 mg/day (n = 227) or gefitinib 250 mg/day (n = 225).

The patient's perspective on treatment with dacomitinib: patient-reported outcomes from the Phase III trial ARCHER 1050.

Patient-reported symptoms, functioning and overall quality of life (QoL) were compared between dacomitinib and gefitinib in ARCHER 1050. Patients (n = 448) with advanced mutation-positive non-small-cell lung cancer completed the EORTC-QLQ-C30 questionnaire and its lung-specific module, LC-13. Mean scores over time were analyzed using a mixed model for repeated measures.

Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors - A territory-wide cohort study.

Background: Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancers. We aimed to evaluate the incidence and prognostic impact of hepatic adverse events (AEs) in a territory-wide cohort of patients who received ICIs.

Methods: Patients were identified from a territory-wide database who received ICIs in 2014-2018.

Distinct Molecular Landscape of Epstein-Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing.

Pulmonary lymphoepithelioma-like carcinoma (LELC) is a subtype of non-small cell lung cancer (NSCLC) characterized by marked lymphocytic infiltration and association with Epstein-Barr virus (EBV). The molecular basis underlying the disease remains unclear. We sought to study the molecular landscape by multiple approaches including whole genomic sequencing, capture-based targeted sequencing, fluorescent in situ hybridization and immunohistochemistry.

Effects of dose modifications on the safety and efficacy of dacomitinib for mutation-positive non-small-cell lung cancer.

We evaluated reasons for dacomitinib dose reduction (DR) and examined adverse event (AE) incidence, key efficacy end points (progression-free survival [PFS]/overall survival [OS]), and pharmacokinetics in dose-reducing patients in the ARCHER 1050 trial. Newly diagnosed patients with mutation-positive, advanced non-small-cell lung cancer received oral dacomitinib (45 mg once-daily [QD]), with stepwise toxicity-managing DR (30 and 15 mg QD) permitted. Skin toxicities (62.

Management of common adverse events related to first-line dacomitinib use in mutation-positive non-small-cell lung cancer: a pooled safety analysis.

This pooled safety analysis was conducted to analyze incidence and management of key dacomitinib-associated adverse drug reactions (ADRs). Patients with mutation-positive advanced non-small-cell lung cancer who received first-line dacomitinib at the 45 mg/day recommended starting dose were included. ADRs were identified based on reasonable association with EGFR tyrosine kinase inhibitors.

Therapeutic Strategies in EGFR Mutant Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) harboring epidermal growth receptor (EGFR) mutation has distinct genomic characteristics. Introduction of systemic treatments that specifically targeted actionable EGFR mutations has changed the therapeutic paradigm in this group of patients. Moreover, newer generations of EGFR tyrosine-kinase inhibitors (EGFR-TKIs) with superior pharmacokinetics and pharmacodynamics properties such as dacomitinib and osimertinib, when used in the front-line setting, have shown more favorable treatment outcomes than first-generation EGFR-TKIs.

Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer.

Introduction: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population.