Final Analysis Data and Exploratory Biomarker Analysis of a Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib Monotherapy for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: The WJOG9717L Study.

Introduction: EGFR tyrosine kinase inhibitors have been the standard treatment for patients with NSCLC who have sensitive mutations. This study revealed final analysis survival data, biomarkers, and resistance mechanisms of osimertinib plus bevacizumab or osimertinib monotherapy in previously untreated patients with advanced -positive nonsquamous NSCLC.

Methods: We previously reported the primary results of a randomized, open-label, phase 2 study comparing osimertinib plus bevacizumab with osimertinib monotherapy for this population.

A phase II study of weekly carboplatin and concurrent radiotherapy in older adults with locally advanced non-small cell lung cancer (LOGIK1902).

Background: Concurrent chemoradiotherapy is the standard therapy for locally advanced non-small cell lung cancer (NSCLC). However, there is little evidence supporting its use in older adults. Low-dose daily carboplatin combined with thoracic radiotherapy is considered a standard regimen for this population.

The Utility and Limitations of Universal Polymerase Chain Reaction Screening for SARS-CoV-2 During Hospital Admission.

Objective: Universal polymerase chain reaction (PCR) screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admission is an effective approach to preventing coronavirus disease 2019 (COVID-19) outbreaks in medical facilities. However, false-positive test results due to a recent infection are a concern. We investigated the usefulness and limitations of universal PCR screening for SARS-CoV-2 on hospital admission in a real-world setting.

TP53 gain-of-function mutations promote osimertinib resistance via TNF-α-NF-κB signaling in EGFR-mutated lung cancer.

EGFR tyrosine kinase inhibitors (TKIs) are effective against EGFR-mutated lung cancer, but tumors eventually develop resistance to these drugs. Although TP53 gain-of-function (GOF) mutations promote carcinogenesis, their effect on EGFR-TKI efficacy has remained unclear. We here established EGFR-mutated lung cancer cell lines that express wild-type (WT) or various mutant p53 proteins with CRISPR-Cas9 technology and found that TP53-GOF mutations promote early development of resistance to the EGFR-TKI osimertinib associated with sustained activation of ERK and expression of c-Myc.

Osimertinib readministration for central nervous system metastases in non-small cell lung cancer positive for EGFR activating mutations.

Background: Osimertinib shows pronounced efficacy for EGFR mutation-positive non-small cell lung cancer (NSCLC) including associated central nervous system (CNS) metastases. Tumors inevitably develop resistance to the drug, however. Osimertinib is sometimes readministered after completion of standard chemotherapy.

Nintedanib plus Chemotherapy for Small Cell Lung Cancer with Comorbid Idiopathic Pulmonary Fibrosis.

A fatal acute exacerbation (AE) occasionally develops during chemotherapy for small cell lung cancer (SCLC) with comorbid idiopathic pulmonary fibrosis (IPF). This study aimed to assess the safety and efficacy of carboplatin, etoposide, and nintedanib combination therapy for unresectable SCLC with comorbid IPF. The NEXT-SHIP study is a multicenter, single-arm, phase 2 trial for unresectable SCLC with IPF (Japan Registry of Clinical Trials registry number jRCTs031190119).

YAP mediates resistance to EGF-induced apoptosis in EGFR-mutated non-small cell lung cancer cells.

Mechanisms underlying the growth and survival of non-small cell lung cancer (NSCLC) cells positive for activating mutations of the epidermal growth factor receptor gene (EGFR) have remained unclear. We here examined the functional relation between such mutant forms of EGFR and Yes-associated protein (YAP), a transcriptional coactivator of the Hippo signaling pathway that regulates cell proliferation and survival. Under the condition of serum deprivation, epidermal growth factor (EGF) induced activation of YAP in NSCLC cell lines positive for mutated EGFR but not in those wild type (WT) for EGFR.

Pooled Analysis of Studies Evaluating Fosnetupitant and Risk Factors for Cisplatin-Induced Nausea and Vomiting During the Extended Overall Phase.

Introduction: Fosnetupitant is a novel neurokinin 1 receptor antagonist (NKRA) with favorable antiemetic efficacy in patients receiving emetogenic chemotherapy. This study assessed the efficacy of fosnetupitant in combination with palonosetron and dexamethasone and identified risk factors for chemotherapy-induced nausea and vomiting (CINV) for up to 168 h after treatment using pooled data from Japanese studies.

Methods: A pooled analysis of randomized phase II and phase III studies was performed to compare the efficacy of fosnetupitant and fosaprepitant in patients receiving cisplatin-based chemotherapy.

MicroRNA-326 negatively regulates CD155 expression in lung adenocarcinoma.

Treatment with immune checkpoint inhibitors induces a durable response in some patients with non-small-cell lung cancer, but eventually gives rise to drug resistance. Upregulation of CD155 expression is implicated as one mechanism of resistance to programmed death receptor-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors, and it is therefore important to characterize the mechanisms underlying regulation of CD155 expression in tumor cells. The aim of this study was to identify microRNAs (miRNAs) that might regulate CD155 expression at the posttranscriptional level in lung cancer.

Regulation of PD-L1 expression in non-small cell lung cancer by interleukin-1β.

Introduction: Programmed cell death-ligand 1 (PD-L1) is a biomarker for prediction of the clinical efficacy of immune checkpoint inhibitors in various cancer types. The role of cytokines in regulation of PD-L1 expression in tumor cells has not been fully characterized, however. Here we show that interleukin-1β (IL-1β) plays a key role in regulation of PD-L1 expression in non-small cell lung cancer (NSCLC).

Evaluation of appropriate conditions for Oncomine DxTT testing of FFPE specimens for driver gene alterations in non-small cell lung cancer.

Background: The Oncomine Dx Target Test Multi-CDx System (ODxTT) is a next-generation sequencing panel approved as a companion diagnostic for drugs targeted to corresponding gene alterations in non-small cell lung cancer. However, appropriate slide conditions for ODxTT have remained unclear.

Methods: We focused on the production of the number of tumor cells on a formalin-fixed paraffin-embedded (FFPE) section and the number of prepared slides, designated the TS value, and determined a TS value of ≥4000 as a target slide condition for ODxTT.

Impact of increased plasma levels of calreticulin on prognosis of patients with advanced lung cancer undergoing combination treatment of chemotherapy and immune checkpoint inhibitors.

Background: Damage-associated molecular pattern (DAMP)-related immunogenic cell death triggers secondary adaptive immune responses. The relationship between DAMP levels and prognosis in patients with non-small cell lung cancer (NSCLC) who undergo a combination therapy of immune checkpoint inhibitors (ICI) and chemotherapy remains unclear.

Methods: Serial plasma samples were prospectively collected from 45 patients treated with ICI combination therapy for advanced NSCLC.

TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC.

Pembrolizumab monotherapy is a standard first-line treatment for PD-L1-high advanced non-small-cell lung cancer (NSCLC) without actionable genomic alterations (AGA). However, few patients experience long-term disease control, highlighting the need for more effective therapies. Datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2-directed antibody-drug conjugate, showed encouraging safety and antitumor activity with pembrolizumab in advanced NSCLC.

Pleuroparenchymal fibroelastosis secondary to autologous peripheral blood stem cell transplantation: A case report.

Pleuroparenchymal fibroelastosis (PPFE) is a rare form of interstitial pneumonitis. Although most cases of PPFE are idiopathic, some cases of PPFE occur secondary to stem cell transplantation. We report a 41-year-old woman developed pneumonia after autologous peripheral blood system cell transplantation (PBSCT).

Gumarontinib in patients with non-small-cell lung cancer harbouring exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial.

Background: Approximately 3-4% of patients with non-small-cell lung cancer (NSCLC) have exon 14 (ex14) skipping mutations. We report primary results from the phase 2 stage of a phase 1b/2 study of gumarontinib, a selective, potent, oral MET inhibitor, in patients with ex14 skipping mutation-positive (ex14-positive) NSCLC.

Methods: The single-arm, multicentre, open-label, phase 2 stage of the GLORY study was conducted at 42 centres across China and Japan.

Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS mutation: a randomised, open-label, phase 3 trial.

Background: Sotorasib is a specific, irreversible inhibitor of the GTPase protein, KRAS. We compared the efficacy and safety of sotorasib with a standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRAS mutation who had been previously treated with other anticancer drugs.

Methods: We conducted a randomised, open-label phase 3 trial at 148 centres in 22 countries.

Association of thyroid transcription factor-1 (TTF-1) expression with efficacy of PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in advanced non-squamous non-small cell lung cancer.

Background: Thyroid transcription factor-1 (TTF-1) expression in advanced non-squamous non-small cell lung cancer (NSCLC) has been associated with the efficacy of pemetrexed plus platinum chemotherapy. However, the relation between TTF-1 expression and efficacy of the combination of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors plus pemetrexed and platinum chemotherapy, a standard first-line treatment regimen for advanced non-squamous NSCLC, has remained unclear.

Methods: We retrospectively evaluated TTF-1 expression in tumor tissue of patients with advanced or recurrent non-squamous NSCLC treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in the first-line setting.

Mutant forms of EGFR promote HER2 trafficking through efficient formation of HER2-EGFR heterodimers.

Introduction: Human epidermal growth factor receptor 2 (HER2) forms homodimers and is retained at the surface of cancer cells positive for HER2 amplification. The dimerization, internalization, and intracellular trafficking of HER2 in cancer cells without HER2 amplification have remained uncharacterized, however.

Materials And Methods: HER2 homodimers and heterodimers were detected in various cell lines with the use of an in situ proximity ligation assay.

Immunostimulatory oncolytic activity of coxsackievirus A11 in human malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive solid cancer with a poor prognosis, whereas coxsackievirus A11 (CVA11) is a potential oncolytic virus for cancer treatment. We here investigated the oncolytic activity of CVA11 with human MPM cell lines. CVA11 infection was cytotoxic in all six MPM cell lines examined and showed no or minimal cytotoxicity toward normal human normal cell lines.