Lorlatinib Tolerability and Association With Clinical Outcomes in Patients With Advanced - or -Rearranged NSCLC: A Brief Report.

Introduction: Treatment with lorlatinib for patients with advanced - and -rearranged NSCLC (+ and + NSCLC) is associated with a unique set of adverse events (AEs) often requiring dose reduction. However, the impact of dose reductions on outcomes remains unclear and is mainly limited to analyses from prospective studies of lorlatinib in the first-line setting.

Methods: We reviewed the course of 144 patients with advanced or -rearranged NSCLC treated with lorlatinib in the second-line or later setting to assess the frequency of dose reductions resulting from treatment-related AEs (TRAEs) and the association between dose reductions and progression-free survival (PFS) and overall survival (OS).

A Safety Analysis of Programmed Death 1 Pathway Inhibitors in Patients With Solid Tumor Malignancies and Preexisting Autoimmune Disease.

Objective: The aim of this study was to characterize the safety of programmed death 1 inhibitors in patients with preexisting autoimmune disease.

Methods: A medical records review study was conducted on adults with solid tumor malignancies who received ≥1 dose of pembrolizumab or nivolumab at Emory Healthcare from September 4, 2014 until December 31, 2019. All autoimmune patients were included (n = 77), whereas the nonautoimmune patients were randomized and the first 156 patients were included in a 2:1 ratio to autoimmune patients.

Retrospective Study of Bleeding Risk with Concomitant Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor and Anticoagulation.

Background: Patients with cancer are at higher risk for venous thromboembolism (VTE) and bleeding, in turn complicating anticoagulant therapy. An added complexity is the toxicity profile of agents used to treat certain cancers, namely the vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs), which are associated with both thromboembolism and hemorrhages. The purpose of this study was to evaluate whether patients taking concurrent VEGF TKI and therapeutic anticoagulant were at higher risk for bleeding compared with patients taking VEGF TKI alone.

Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: a randomized phase II study.

Background: Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein 4 has achieved modest clinical activity as salvage therapy in relapsed small cell lung cancer (SCLC). We conducted this signal-finding study to assess the efficacy of ICB with or without radiation in relapsed SCLC.

Methods: Patients with relapsed SCLC and ≤2 previous lines of therapy were randomized to (1) arm A: durvalumab (D) 1500 mg/tremelimumab (T) 75 mg (intravenously every 4 weeks without stereotactic body radiation therapy (SBRT)) or (2) arm B: immune-sensitizing SBRT to one selected tumor site (9 Gy × 3 fractions) followed by D/T.

Efficacy and safety of immune checkpoint blockade in self-identified Black patients with advanced non-small cell lung cancer.

Background: To the authors' knowledge, race-based differences in efficacy for the treatment of patients with advanced non-small cell lung cancer (NSCLC) have not been studied to date due to the underrepresentation of patients of minority backgrounds in pivotal trials. In the current study, the authors examined real-world differences in outcome in a diverse patient population.

Methods: The authors retrospectively analyzed the clinical outcomes of patients with advanced NSCLC who were treated with single-agent immune checkpoint blockade (ICB) between 2013 and July 2018 at Winship Cancer Institute of Emory University in Atlanta, Georgia.

Afatinib for the treatment of mutation-positive NSCLC: A review of clinical findings.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors represent the standard of care in patients with mutation-positive (m+) non-small cell lung cancer (NSCLC). The availability of several EGFR tyrosine kinase inhibitors approved for use in the first-line or later settings in NSCLC warrants an in-depth understanding of the pharmacological properties of, and clinical data supporting, these agents. The second-generation, irreversible ErbB-family blocker, afatinib, has been extensively studied in the context of m+ NSCLC.

Alectinib and Brigatinib: New Second-Generation ALK Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

The treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the discovery of genetic driver mutations and associated targeted therapies. Anaplastic lymphoma kinase () mutations are present in about 5% of NSCLC cases, and treatment with the first-generation ALK inhibitor crizotinib has shown better progression-free survival (PFS) and response rate compared to traditional chemotherapy. However, eventually, -mutated NSCLC develops resistance to treatment with crizotinib, and second-generation ALK inhibitors such as ceritinib, brigatinib, and alectinib have been shown to be effective in the second-line setting after progression on crizotinib.

Tacrolimus for the treatment of immune-related adverse effects refractory to systemic steroids and anti-tumor necrosis factor α therapy.

Immunotherapy treatments in oncology have garnered much attention and use throughout the past several years. With increased use and new approvals in many different types of solid tumors and hematological malignancies, practitioners in oncology should have an appreciation and understanding of the potential adverse effects of these unique treatment approaches. The most common adverse effects with immunotherapy treatment are immune-related adverse effects with activation of patients' immune systems against a wide array of tissues and organ systems.

Affinity purification of the tobacco plastid RNA polymerase and in vitro reconstitution of the holoenzyme.

We affinity-purified the tobacco plastid-encoded plastid RNA polymerase (PEP) complex by the alpha subunit containing a C-terminal 12 x histidine tag using heparin and Ni(2+) chromatography. The composition of the complex was determined by mass spectrometry after separating the proteins of the >900 kDa complex in blue native and SDS polyacrylamide gels. The purified PEP contained the core alpha, beta, beta', beta" subunits and five major associated proteins of unknown function, but lacked sigma factors required for promoter recognition.

Identification and analysis of a conserved immunoglobulin E-binding epitope in soybean G1a and G2a and peanut Ara h 3 glycinins.

To identify conserved immunoglobulin E (IgE)-binding epitopes among legume glycinins, we utilized recombinant soybean G2a and G2a-derived polypeptide fragments. All of these fusion polypeptides bound IgE, and the C-terminal 94-residue fragment appeared to bind more IgE. Using synthetic peptides we identified S219-N233 (S(219)GFAPEFLKEAFGVN(233)) as the dominant IgE-binding epitope.

A nucleus-encoded maize protein with sigma factor activity accumulates in mitochondria and chloroplasts.

Plants contain nuclear gene families that encode proteins related to the principal sigma factors of eubacteria. As sigma factors function in transcription, the plant proteins have been presumed or demonstrated to associate with the eubacteria-like RNA polymerase of chloroplasts. In maize, five sig cDNA sequences have been reported, and four of the products are present in plastids as predicted.

Identification of IgE-binding proteins in soy lecithin.

Background: Soy lecithin is widely used as an emulsifier in processed foods, pharmaceuticals and cosmetics. Soy lecithin is composed principally of phospholipids; however, it has also been shown to contain IgE-binding proteins, albeit at a low level. A few clinical cases involving allergic reactions to soy lecithin have been reported.

Soybean glycinin G1 acidic chain shares IgE epitopes with peanut allergen Ara h 3.

Background: The identification of IgE epitopes for proteins is the first step in understanding the interaction of allergens with the immune system. Proteins from the legume family have shown in vitro cross-reactivity in IgE-binding assays, but this cross-reactivity is rarely clinically significant. Resolution of this discrepancy requires IgE epitope mapping of legume family protein allergens.